Chemically stable KETO-amide-based fibroblast activation protein-targeted conjugates, compositions, and methods of use

Abstract

Keto-amide based FAP-targeted ligands, conjugate comprising same, pharmaceutical compositions comprising same, and methods of use for imaging and treatment.

Description

[0001] CHEMICALLY STABLE KETO-AMIDE-BASED FIBROBLAST ACTIVATION PROTEIN-TARGETED CONJUGATES, COMPOSITIONS, AND METHODS OF USE CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. provisional patent application no.63 / 556,728, which was filed February 22, 2024, and U.S. provisional patent application no.63 / 558,922, which was filed February 28, 2024, both of which are hereby incorporated by reference in their entireties. TECHNICAL FIELD The present disclosure relates to fibroblast activation protein (FAP) ligands, conjugates comprising same, compositions comprising the conjugates, and methods of use. BACKGROUND Fibroblast activation protein (FAP) is characterized as a type-II, membrane-bound serine protease responsible for cleaving proline-amino acid peptide bonds. Its expression is notably identified on cancer-associated fibroblasts (CAFs) and myofibroblasts engaged in collagen production. Consequently, there has been an emergence recently of reported FAP-targeted drugs and imaging agents designed for applications in cancer and other fibrotic diseases. While several small molecule ligands targeting FAP are available, recently disclosed FAP-targeted ligands have encountered challenges related to chemical instability, particularly under acidic or basic conditions and / or under reaction conditions involving heat, resulting in the formation of undesired side products, leading to their accumulation in healthy tissues, such as the liver and spleen; etc. Conjugates comprising such FAP-targeted ligands are plagued by short tumor retention and, consequently, poor signal to background ratios. To address these issues, a new FAP-targeted ligand is disclosed, which is referred to as FAP9. Notably, FAP9 demonstrates enhanced stability under both acidic and basic conditions, while maintaining binding affinity that is similar to, or better than, that of previously disclosed FAP-targeted ligands. In view of the foregoing, it is an object of the present disclosure to provide conjugates comprising FAP9, compositions comprising same, and methods of use in the targeted delivery of drugs and imaging agents, such as S0456. This and other objects and advantages will be apparent from the detailed description provided herein. SUMMARY Provided is a conjugate of formula I or formula II: wherein A is a ligand having a structure of formula IX or L is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and an optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio- sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; and C is a pharmacokinetic (PK) extender; and wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the functionalized 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic heterocycle, a primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1 is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6alkyl, -O-C1-6alkyl, -S-C1-6alkyl, Cl-Cl0alkyl, C3-Cl0cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6and R7are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6alkyl, -O-C1-6alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11 are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6alkyl, -O-C1-6alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12is selected from the group of substituents consisting of -H, -D, -F, -C1-C6alkyl, -C(O)CH3, and -Cl-Cl0alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13is selected from the group of substituents consisting of -H, -D, Cl-Cl0alkyl, -C3-Cl0cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally independently substituted and the aryl in C7-C20 alkyl aryl is: R13is selected from the group consisting of -H, -D, -halo, and Cl-C4alkyl, which is optionally substituted, and R14, R15, R16, and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted; or R13 is and R22 are independently selected from the group of - - -OMe, -C1-C3 alkyl, benzyl (Ph-CH2-), and substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted; and stereoisomers, pharmaceutically acceptable salts, and hydrates thereof. In some embodiments, A has the structure of formula III:

[0002] In certain embodiments, R13 is . L can comprise -(O−CH2−CH2)n- where n is an integer from 1-11. B can comprise an optical imaging agent. In some embodiments, B comprises optical imaging agent S0456, which has the structure: ;

[0003] or . Some conjugates comprise the structure: F F O OMe . In another aspect, the disclosure concerns methods of imaging cancer or fibrosis in a patient, which method comprises administering to the patient a conjugate and imaging the cancer or the fibrosis in the patient. The disclosure also concerns methods of treating cancer or inflammation in a patient comprising administering to the patient an effective amount of a conjugate disclosed herein, whereupon the patient is treated for cancer or inflammation. In another aspect, the disclosure concerns conjugates for use in a method of treating cancer or inflammation. In a further aspect, the disclosure concerns conjugates for use in imaging of cancer or fibrosis in a patient. In yet another aspect, the disclosure concerns methods of imaging cancer or fibrosis in a patient, which method comprises (i) administering to the patent a combination of near infrared (NIR) imaging agents comprising (i) (ii)

[0004] / or (ii) imaging the cancer or the fibrosis in the patient. In some embodiments, the dose of NIR imaging agents is about 3 to about 5 nmol (such as about 3 to 5 nmol, 3 to about 5 nmol, or 3-5 nmol). In certain embodiments, A has the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:

[0005]

[0006] where R1 is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6alkyl, -O-C1-6alkyl, -S-C1-6alkyl, -Cl-Cl0alkyl, -C3-Cl0cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26 are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted. R13is selected from the group of substituents consisting of O O O O O O Some conjugates have the formula A-L-B, wherein A is a fibroblast activation protein alpha (FAP^) targeting ligand having a structure of formula (I) or (II):

[0007] . .

[0008] ;

[0009] H OH H OH N or protein-binding ligand, a hapten, or an internalization-inducing peptide. In some embodiments, at least one of B, B’ and B” comprises a fluorescent dye. In certain embodiments, at least one of B, B’ and B” comprises a radioisotope / radionuclide for radio-imaging, radiotherapy, or magnetic resonance imaging (MRI). The radioisotope / radionuclide can selected from the group consisting of177Lu,90Y,211At,225Ac,161Tb,18F,32P,44Sc,47Sc,52Mn,55Co,64Cu,67Cu,67Ga,68Ga,86Y,89Sr,89Zr,99mTc,111In,114mIn,117mSn,124I,125I,131I,149Tb,153Sm,152Tb,155Tb,169Er,186Re,188Re,212Pb,212Bi,213Bi,223Ra,224Ra,225Ac,161Tb, and227Th. In some embodiments, the radioisotope / radionuclide is selected from the group consisting of11C,13C,13N,15O,60Co, and123I. In other embodiments, at least one of B, B’ and B” is or comprises a radiolabeled prosthetic group selected from the group consisting of: comprises a chelating group selected from DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or a derivative thereof; S- 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) or derivative thereof; 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) or a derivative thereof; [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]- trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (p-SCN-Bn-CHX-A”-DTPA) or a derivative thereof; TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) or a derivative thereof; SarAr (1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane- 1,8-diamine or a derivative thereof; NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) or a derivative thereof; NETA (4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl- [1,4,7]triazonan-1-yl) acetic acid or a derivative thereof; TRAP (1,4,7-triazacyclononane-1,4,7- tris[methyl(2-carboxyethyl)phosphinic acid) or a derivative thereof; HBED (N,N0-bis(2- hydroxybenzyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; 2,3-HOPO (3- hydroxypyridin-2-one) or a derivative thereof; PCTA (3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca- 1(15),11,13-triene-3,6,9,-triacetic acid) or a derivative thereof; DFO (desferrioxamine) or a derivative thereof; DTPA (diethylenetriaminepentaacetic acid) or a derivative thereof; OCTAPA (N,N0-bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; H2-MACROPA (N,N'-bis[(6-carboxy-2-pyridipmethyl]-4,13-diaza-18-crown-6) or a derivative thereof; H2dedpa (1,2-[[carboxy)-pyridin-2-yl]-methylamino]ethane or a derivative thereof; and EC20-head comprising β-l-diaminopropionic acid, aspartic acid, and cysteine, wherein the chelating group optionally chelates a metal. In certain embodiments, at least one of B, B’ and B” comprises a nuclide for positron emission tomography (PET) or single-photon emission computed tomography (SPECT). L can comprise one or more of an amino acid, a polyethylene glycol (PEG) monomer, a PEG oligomer, a PEG polymer, a polylactone, a polymethylmethacrylate, a polyoxymethylene, a heterocycle, or any combination of two or more thereof. In some aspects, the disclosure concerns pharmaceutical compositions comprising a conjugate and a pharmaceutically acceptable carrier. In another aspect the disclosure concerns ligands that targets fibroblast activation protein alpha (FAP^), wherein the ligand has the structure of formula (IX) or formula (X):

[0010] (IX) (X) and a molecular weight below 10,000; L is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio- sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; C is a pharmacokinetic (PK) extender; and wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the functionalized 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic heterocycle, a primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11 are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13 is selected from the group of substituents consisting of -H, -D, Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20alkyl aryl is: is selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which is optionally substituted, and R14, R15, R16, and R17are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted; or R13 is and R22 are independently selected from the group of substituents consisting of -H, -D, -OMe, -C1-C3alkyl, benzyl (Ph-CH2-), substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted. FIGURES Fig.1 shows the rational for the design of fibroblast activation protein ligand 9 (FAP9 ligand). Fig.2 shows the synthesis of FAP9 ligand with free amine (14). Fig.3 shows the synthesis of FAP9-FITC (fluorescein isothiocyanate) conjugate (15). Fig.4 shows the synthesis of FAP9-PEG3-NOTA (17), FAP9-PEG3-DOTA (18), and FAP9-PEG3-Bn-DOTA (19) conjugates. Fig.5 shows the synthesis of FAP9-PEG3-IP-NOTA (22), FAP9-PEG3-DOTA (23), and FAP9-PEG3-IP-Bn-DOTA (24) conjugates. Fig.6 shows the synthesis of FAP9-LyCOOH-IP-Bn-DOTA (28) (Ly = lysine; IP = iodophenyl; Bn = Benzyl). Fig.7 shows the synthesis of 30a and 31. Fig.8 shows the synthesis of FAP9-Ly-IP-NOTA (32), FAP9-Ly-IP-DOTA (33), FAP9- Ly-IP-Bn-DOTA (34), FAP9-Ly-IP-Bn-MACROPA (36), and FAP9-Ly-IP-3p- C-NETA (37) conjugates. Fig.9 shows the synthesis of FAP9-Pz-IP-NOTA (41), FAP9-Pz-IP-DOTA (42), FAP9- Pz-IP-Bn-DOTA (43), FAP9-Pz-IP-MACROPA (44), and FAP9-Pz-IP-3p-C-NETA (45) conjugates (Pz = Piperazine). Fig.10 shows the synthesis of fibroblast activation protein ligand 10 (FAP10 ligand)-Bn- DOTA (53) and FAP10-IP-Bn-DOTA (55) conjugates. Fig.11 shows the synthesis of FAP9-PEG1-NOTA (57), FAP9-PEG1-DOTA (58), and FAP9-PEG1-Bn-DOTA (59) conjugates. Fig.12 shows the synthesis of FAP9 with lysine (62), PEG1 (63) and Pz (64) linkers and the radiosensitizer nitro imidazole (ImNO2 = nitro imidazole). Fig.13 shows the synthesis of FAP9-Ly-ImNO2-NOTA (65), FAP9-Ly-ImNO2-DOTA (66) and FAP9-Ly-ImNO2-Bn-DOTA (67) conjugates. Fig.14 shows the synthesis of FAP9-PEG1-ImNO2-NOTA (68), FAP9-PEG1-ImNO2- DOTA (69), and FAP9-PEG1-ImNO2-Bn-DOTA (70) conjugates. Fig.15 shows the synthesis of FAP9-Pz-ImNO2-NOTA (71), FAP9-Pz-ImNO2-DOTA (72), and FAP9-Pz-ImNO2-Bn-DOTA (73). Fig.16 shows the synthesis of FAP9-PEG3-ICG conjugate (74) Fig.17 shows the synthesis of FAP9-Ly-ICG conjugate (75). Fig.18 shows the synthesis of FAP9-PEG2-IP-S0456 conjugate (77). Fig.19 shows the docking of FAP9 base ligand with human fibroblast activation protein alpha (FAPα) (PDB number: 1Z68). Fig.20 shows the docking of different FAP9 analogues with human FAPα (PDB number: 1Z68), wherein (A) is FAP8, (B) is with methyl, (C) is with ethyl, (D) is with propyl, (E) is with butyl, and (F) is with fluoro substitution. Fig.21 shows the docking of FAP10 with human FAPα (PDB number: 1Z68). Fig.22 shows the binding analysis of FAP9-FITC (15) and FAP8-FITC conjugates on HEK-hFAP cells. Fig.23 shows the FAP9-PEG3-FITC internalization in HT1080-hFAP cells. Fig.24 shows the binding analysis of [111In] In-FAP9-Ly-IP-Bn-DOTA (34) and [111In] In-FAP9-IP-Bn-DOTA (24) conjugates on HEK-hFAP cells. Fig.25 shows the enzyme inhibition assay results of FAP9-Ly-IP-Bn-DOTA (34) with human purified FAP (repeated three times with different batches of compound), PREP and DPP-IV. Fig.26 shows the radio HPLC chromatogram of FAP9-Ly-IP-Bn-DOTA (34) chelation with177LuCl3. Fig.27 shows the stability of lutetium-labelled FAP9-Ly-IP-Bn-DOTA conjugate ([177Lu] Lu-FAP9-Ly-IP-Bn-DOTA) in formulation solution. Fig.28 shows the stability of FAP9-Ly-IP-Bn-DOTA (34) conjugate incubated with human and mouse plasma. Fig.29 shows the SPECT radio-imaging, biodistribution and dosimetry analysis of [111In] In-FAP9-Ly-IP-Bn-DOTA (34) in 4T1 tumor-bearing mice. Fig.30 shows the SPECT / CT radio-imaging and biodistribution analysis of [111In] In- FAP9-Ly-IP-Bn-DOTA (34) in 4T1 tumor-bearing mice. Fig.31 shows the SPECT / CT imaging of [111In] In-FAP9-Ly-IP-SCN-DOTA (34) conjugate in 4T1 tumor-bearing mice as function of time. Fig.32 shows the SPECT radio-imaging of [111In] In-FAP9-Ly-IP-Bn-DOTA (34) conjugated in U87Mg tumor-bearing mice (Mouse 1 and Mouse 2). Fig.33 shows the SPECT radio-imaging of [111In] In-FAP9-Ly-IP-Bn-DOTA (34) conjugate in RENCA tumor-bearing mice (Mouse 1 and Mouse 2). Fig.34 shows the SPECT radio-imaging of [111In] In-FAP2286 conjugate in RENCA tumor-bearing mice. Fig.34a shows the SPECT radio-imaging of [111In] In-FAP9-NADS-Bn-DOTA conjugate in 4T1 tumor-bearing mice. Fig.35 shows the ex vivo biodistribution analysis of 4T1 tumor-bearing mice injected with [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA (34) (A). Dosimetry and tumor: healthy tissues ratios in 4T1 tumor-bearing mice injected with [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA conjugate (B). Fig.36 (A) shows the recommended dosimetry for healthy tissues as per FAD guidelines [1-3], along with the tumor-responsive dosimetry. (B) shows the tumor-to-healthy tissue ratios achieved by [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA and the ratios required for treating radiosensitive and highly radioresistant tumors. Fig.37 shows the tumor growth inhibition, body weight changes, and overall survival rates of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA radioligand therapy in MDA-MB-231 (human breast) tumor-bearing mice. Fig.38 shows the tumor growth inhibition, body weight changes and overall survival rates of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA radioligand therapy in 4T1 (mouse breast) tumor- bearing mice. Fig.39 shows the tumor growth inhibition, body weight changes and overall survival rates of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA radioligand therapy in PANC-1(human pancreatic) tumor-bearing mice. Fig.40 shows the tumor growth inhibition, body weight changes and overall survival rates of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA radioligand therapy in HT-29 (human colorectal) tumor-bearing mice. Fig. 41 shows the head-to-head radioligand therapy comparison of [177Lu] Lu-FAP9-Ly- IP-Bn-DOTA (34) with [177Lu] Lu-FAP2286 (tumor growth inhibition, body weight changes and overall survival rates) in U87MG (human glioblastoma) tumor-bearing mice. Fig. 42 shows the representative micrographs of 4-mm hematoxylin- and eosin-stained (H&E) sections of fixed heart, lungs, liver, spleen and kidney tissues after administration of control (injected with PBS) or [177Lu]Lu-FAP9-Ly-IP-Bn-DOTA in HT29 tumor– bearing mice. Fig. 43 shows the SPECT radio-imaging of [111In] In-FAP9-PEG3-IP-Bn-DOTA (24), biodistribution (top panel), dosimetry and tumor-to-healthy tissues ratios (bottom panel) in 4T1 tumor-bearing mice. Fig. 44 shows the biodistribution and tumor: healthy tissues ratios of [177Lu] Lu-FAP10- IP-Bn-DOTA (51) (left panel) and [177Lu] Lu-FAP10-Bn-DOTA (49) (right panel) in 4T1 tumor-bearing mice. Fig.45 LC-MS spectrum of FAP9-Ly-IP-DOTA (33). Fig.46 LC-MS spectrum of FAP9-Ly-IP-Bn-DOTA (34). Fig.47a shows the prophetic synthetic scheme and structure of FAP9 conjugates having different heterocyclic rings in the linker part. Fig.47b shows the prophetic synthetic scheme and structure of FAP9 conjugates having different aliphatic cyclic diamino rings in the linker part. Fig.47c shows the prophetic synthetic scheme and structure of FAP9 conjugates having a different combination of acyclic and cyclic linkers. Fig.47d shows the prophetic synthetic scheme and structure of FAP9 conjugates having different functionalized linkers. Fig.47e shows the prophetic synthetic scheme and structure of FAP9 conjugates having different functionalized linkers. Fig.47f shows the prophetic synthetic scheme and structure of FAP9 conjugates having different bio-reactive functionalities in the linker part. Fig.47g shows the prophetic synthetic scheme and structure of FAP9 conjugates having different bio-reactive functionalities in the linker part. FIG.48 presents a schematic of the synthesis of FAP9-S0456 conjugate (15). FIG.49 presents a schematic of the synthesis of FAP9-S0456 with different PEG lengths. Fig.50 shows the binding analysis of FAP9-S0456 conjugate on FAP-expressing (HEK- hFAP) cells. Fig.51 shows in vivo whole-body optical imaging and biodistribution of FAP9-S0456 conjugate in HT29 tumor bearing mice (n = 3). As shown in the fluorescence images, targeted mice were injected with a dose (5 nmol / mouse) of FAP9-S0456 conjugate (16), whereas competition mice were co-injected with FAP9-S0456 conjugate + 200-fold excess of compound 15b. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.52 shows in vivo whole-body optical imaging and biodistribution of FAP9-S0456 conjugate in KB tumor-bearing mice (n = 3). As shown in the fluorescence images, targeted mice were injected with a dose (5 nmol / mouse) of FAP9-S0456 conjugate (16), whereas competition mice were co-injected with FAP9-S0456 conjugate + 200-fold excess of compound 15b. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.53 shows in vivo whole-body optical imaging and biodistribution of FAP9-S0456 conjugate in 4T1 tumor-bearing mice (n = 3). As shown in the fluorescence images, targeted mice were injected with a dose (5 nmol / mouse) of FAP9-S0456 conjugate (16), whereas competition mice were co-injected with FAP9-S0456 conjugate + 200-fold excess of compound 15b. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.54 shows in vivo whole-body optical imaging and biodistribution of FAP9-S0456 conjugate in MDA-MB-231 tumor-bearing mice (n = 3). As shown in the fluorescence images, targeted mice were injected with a dose (5 nmol / mouse) of FAP9-S0456 conjugate (16), whereas competition mice were co-injected with FAP9-S0456 conjugate + 200-fold excess of compound 15b. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.55 shows in vivo whole-body optical imaging and biodistribution comparison of FAP8-S0456 vs. FAP9-S0456 in HT29 tumor-bearing mice (n = 3) at four hours post-injection. Fig.56 shows the quantification of fluorescence intensity of tumor and other healthy tissues and corresponding tumor: healthy tissue ratios between FAP8-S0456 vs. FAP9-S0456 conjugates. Fig.57 shows the whole body and biodistribution imaging results of FAP9-S0456 across five different tumor models (HT29, KB, 4T1, MDA-MB-231 and U87 MG) in mice injected with FAP9-S0456 (targeted) and FAP9-S0456 +200-fold excess of unlabeled FAP9 (competition). Fig.58 shows the dose escalation study results of FAP9-S0456 conjugate in 4T1 tumor bearing mice (n = 3) injected with three different doses of FAP9-S0456 (3 nmol, 5nmol and 10 nmol / mouse). The whole-body and biodistribution images were acquired at 4 hours post- injection. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.59 shows the quantification of fluorescence intensity of tumors and other healthy tissues and corresponding tumors: healthy tissue ratios of among different doses in 4T1 tumors. Fig.60 shows the dose escalation study results of FAP9-S0456 conjugate in RENCA tumor bearing mice (n = 3) injected with three different doses of FAP9-S0456 (3 nmol, 5nmol and 10 nmol / mouse). The whole-body and biodistribution images were acquired at 4 hours post- injection. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.61 shows the quantification of fluorescence intensity of tumors and other healthy tissues and corresponding tumors: healthy tissue ratios of among different doses in RENCA tumors. Fig.62 shows in vivo whole-body optical imaging and biodistribution of FAP9-S0456 conjugate in CT26 tumor-bearing mice (n = 3) injected with 5 nmol / mouse of FAP9-S0456 conjugate. The tissues examined from top to bottom are tumor, heart, lungs, liver, spleen, stomach, small intestine, kidneys, and muscle. Fig.63 shows the quantification of fluorescence intensity of tumors and other healthy tissues and corresponding tumors: healthy tissue ratios of among different doses in CT26 tumors. Fig.64 shows the dose escalation study results of FAP9-S0456 conjugate in MDA-MB- 231 tumor bearing mice (n = 3) injected with three different doses of FAP9-S0456 (3 nmol, 5nmol and 10 nmol / mouse). The whole-body and biodistribution images were acquired at 4 hours post-injection. Fig.65 shows the dose escalation study results of FAP9-S0456 conjugate in A549 tumor bearing mice (n = 3) injected with three different doses of FAP9-S0456 (3 nmol, 5nmol and 10 nmol / mouse). The whole-body and biodistribution images were acquired at 4 hours post- injection. Fig.66 shows the dose escalation study results of FAP9-S0456 conjugate in MIA PaCa-2 (pancreatic) tumor-bearing mice (n = 3) injected with FAP9-S0456 (5 nmol / mouse). The whole- body and biodistribution images were acquired at 4 hours post-injection. FIG.67 illustrates dose escalation results for FAP9-S0456 in RENCA tumor-bearing mice. Fig.68 shows dose escalation for OTL38 in RENCA tumor-bearing mice. Fig.69 presents quantification fluorescent intensity and T:healthy tissues ratios for FAP9- S0456 and OTL38 in RENCA tumors. Fig.70 presents cocktail imaging for FAP9-S0456 and OTL38 in RENCA tumors. Fig.71 shows quantification of mean fluorescent intensity for the cocktail with RENCA tumors. Fig.72 presents dose escalation study with OTL-38 in 4T1 tumor-bearing mice. Fig.73 presents quantification of fluorescent intensity for 4T1 tumors. Fig.74 shows dose escalation for OTL38 in RENCA tumor-bearing mice. Fig.75 shows quantification fluorescent intensity and T:healthy tissues ratios for FAP9- S0446 and OTL38 in RENCA tumors. Fig.76 presents imaging with an optimal dose of OTL38 at 4 hours post-injection. Fig.77 presents dose escalation of OTL38 in MDA-MB-231 tumor-bearing mice. Fig.78 presents dose escalation of OTL38 in A549 tumor-bearing mice. Fig.79 shows MIA PaCa-2 tumor imaging 4 hours post-injection for FAP9-S0456 and OTL38. Fig.80 presents imaging of MIA PaCa-2 tumors with combination of FAP9-S0456 and OTL38. Fig.81 presents quantification of fluorescent intensity for FAP9-S0456, OTL38 and the combination. Fig.82 shows cocktail imaging in 4T1 tumors. Fig.83 presents quantification of mean fluorescent intensity of the 4T1 cocktail study. Fig.84 shows cocktail imaging in RENCA tumors. Fig.85 shows imaging of RENCA tumors with the cocktail. Fig.86 presents cocktail imaging in CT26 tumors. Fig.87 shows quantification of fluorescent intensity for CT26 cocktail imaging. Fig.88 shows cocktail imaging of A549 tumors. Fig.89 presents quantification of fluorescent intensity for A549 tumors. Fig.90 presents cocktail imaging of MDA-MB-231 tumors. Fig.91 presents quantification of fluorescent intensity in MDA-MB-231 tumors. Fig.92 presents a comparison of cocktail vs. single agent tumor fluorescence intensities. Fig.93 shows the synthesis of different FAP9-PI3k conjugates (29-31). Fig.94 shows the synthesis of FAP9-PEG3with a cysteine linker (34). Fig.95 shows the synthesis of FAP9-transforming growth factor β (FAP9-TGFβ) conjugates (37-38). Fig.96 shows the synthesis of conjugate (40) with a non-cleavable linker. Fig.97 shows the synthesis of conjugate (43) with a non-cleavable linker. Fig.98 shows the synthesis of different FAP9-PI3k conjugates (47-49) with cathepsin- cleavable linkers. Fig.99 shows the synthesis of different FAP9-TGFβ conjugates (60-63) with cathepsin- cleavable linkers. Fig.100 shows a conjugate with a reductively cleavable linker and a conjugate with an enzymatically cleavable linker. Fig.101 shows examples of ROCK inhibitors, a FAK inhibitor, a PDGFR inhibitor, and VEGFR inhibitors. FIG.102 presents a synthetic scheme to attach various drug moieties to FAB9 moieties. DESCRIPTION The present disclosure is based on the discovery of keto-amide-based ligands that target fibroblast activation protein alpha (FAPα). Incorporation of the ligands into conjugates enable the delivery of active agents to FAPα+ cancer-associated fibroblasts and activated myofibroblasts, such as in the imaging and treatment of cancer, fibrosis, and other inflammatory diseases. Advantages of such conjugates include, but are not limited to, increased tumor retention and better signal-to-background ratios. Fig.1 presents some aspects of the rationale and importance for the design of FAP9 ligand. The introduction of the CH3group avoids cyclization and increases the stability of the molecule to acidic conditions. In addition, the CH3group increases the stability of the molecule to basic conditions, increases the FAP selectivity, increases the affinity to FAP, and increases tumor uptake, retention and tumor-to-healthy tissue ratios. The design also increases FAP selectivity overprolyl oligopeptidase (PREP) and tumor specificity. Importantly, the design increases the therapeutic potential of the conjugate. In view of the above, provided is a conjugate of formula I or formula II: wherein A is a ligand having a structure of formula IX or formula X: L is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and an optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio- sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; and C is a pharmacokinetic (PK) extender; wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the functionalized 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic heterocycle, a primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6alkyl, -O-C1-6alkyl, -S-C1-6alkyl, Cl-Cl0alkyl, C3-Cl0cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6and R7are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6alkyl, -O-C1-6alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13 is selected from the group of substituents consisting of -H, -D, Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20alkyl aryl is: is selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which is optionally substituted, and R14, R15, R16, and R17are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted; or R13 is and R22are independently selected from the group of substituents consisting of -H, -D, -OMe, -C1-C3 alkyl, benzyl (Ph-CH2-), and substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted; and stereoisomers, pharmaceutically acceptable salts, and hydrates thereof. A can have the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:

[0011] wherein n is an integer from 0 to 10, R1is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26 are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted. R13 can be independently selected from the group of substituents consisting of O O O O O O In some embodiments, attachment of A groups is as shown below. Generally, in certain embodiments, attachment of A to the L group is accomplished by bonding at a position on the quinoline moiety.F FOOMeN to the linker FFOOMe to the linker . In some embodiments, a linkercan be attached to the remaining position of the molecule, such as on the dimethoxy benzene ring. In some embodiments, B can comprise (i) a metal chelating group, optionally bound to a metal or a group covalently bound to an isotope, wherein said metal or isotope can be used for radio-imaging, radiotherapy, or magnetic resonance imaging, (ii) a fluorescent imaging agent, (iii) an optical imaging agent, (iv) a photosensitizer, (v) a radiosensitizer, (vi) a chemo-sensitizer, or (vii) an immunotherapeutic agent. The PK extender can be an albumin-binding ligand, a plasma protein-binding ligand, a hapten, or an internalization-inducing peptide. In some embodiments, the conjugate is of the formula A-L-B, wherein A is a fibroblast activation protein alpha (FAP^) targeting ligand having a structure of formula (I) or (II):

[0012] . In certain embodiments, B comprises optical imaging agent S0456, which has the structure: , wherein R32is or

[0013] In some embodiments, the S0456-containing conjugates, such as FAP9-S0456, may be used in combination with Cytalux® (OTL38) to obtain improved NIR imaging results. As detailed below, screening of three different doses of FAP9-S0456 (3 nmol, 5 nmol, and 10 nmol) and three different doses of OTL38 (2 nmol, 5 nmol, and 10 nmol) were undertaken. The results showed that a 5 nmol dose of FAP9-S0456 provided the best tumor-to-healthy tissue ratio, while a 2 nmol dose of OTL38 offered optimal tumor contrast and a favorable tumor-to-healthy tissue ratio. Using these optimal doses, both probes were combined to generate cocktail images, which demonstrated enhanced tumor contrast, and an even better tumor-to-healthy tissue ratio compared to either probe alone. Therefore, in some embodiments, a mixture of 5 nmol FAP9- S0456 and 2 nmol OTL38 will be used for imaging or fluorescence-guided surgery in cancer patients. L can comprise one or more of an amino acid, a polyethylene glycol (PEG) monomer, a PEG oligomer, a PEG polymer, a polylactone, a polymethylmethacrylate, a polyoxymethylene, a heterocycle, or any combination of two or more thereof. L can comprise an oligomer of one or more peptidoglycans, glycans, anions, heterocycles, or any combination of two or more thereof. L can comprise at least one diamino butyric acid group, a substituted benzene group, a lysine group, a 2,3-diaminopropionic acid group, a tyrosine group, a glutamic acid group, a cysteine group, or any combination of two or more thereof. L can comprise an ether, a thioether, a tertiary amine, a C1-6alkyl, piperazine, piperidine, a bicycloheptane, a substituted benzene, or a combination of two or more thereof. L can comprise a moiety of the formula:

[0014] wherein n = 0-10. L can comprise a moiety of the formula: L can comprise a moiety of the formula: . formula: . . L can be a linker that can be cleaved. L can be cleaved reductively, oxidatively, or enzymatically, for example (see Fig.98, for example). L can comprise an oxime ester. L can comprise a hydrazone. L can comprise an enzyme-cleavable linker. L can comprise a PEGn, wherein n = 1-36 or 1-11. L can comprise a peptide. L can comprise a peptidoglycan. L can comprise an alkyl. L can comprise a sugar. L can comprise or can be: . , alkyl-, sugar-, and peptide-based dual linkers. L can be a non-releasable linker. L can be covalently bonded to A and B of formula (I) or A, B and C of formula (II). L can comprise a moiety of the formula: . can be optionally substituted; and z is an integer from 1 to 8. L can comprise: wherei f R29a, R29b, R30a, and R30bis independently H or C1- C6 alkyl, which can be optionally substituted. L can comprise a moiety selected from: H NN O S, ,OO,

[0015]

[0016] . e a fluorescent dye. The fluorescent dye can comprise carbocyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, polymethine, coumarine, rhodamine, xanthene, fluorescein, borondipyrromethane (BODIPY), CyS, CyS.S, Cy7, VivoTag-680, VivoTag-S680, VivoTag-S7S0, AlexaFluor660, AlexaFluor680, AlexaFluor700, AlexaFluor7S0, 10 AlexaFluor790, Dy677, Dy676, Dy682, Dy7S2, Dy780, DyLightS47, Dylight647, HiLyte Fluor 647, HiLyte Fluor 680, HiLyte Fluor 7S0, IRDye 800CW, IRDye 800RS, IRDye 700DX, ADS780WS, ADS830WS, indocyanine green (ICG), an analog of ICG, or ADS832WS. The fluorescent dye can comprise a structure selected from:

[0017] O NH OHO3SO window (1000-1700 nm). The fluorescent dye can be selected from:

[0018]

[0019] B, B’ and B can independently comprise a photosensitizer selected from:

[0020] C N B, B’ and B” can independently comprise a chelating group selected from DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or a derivative thereof; S-2-(4- isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) or derivative thereof; 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p- SCN-Bn-NOTA) or a derivative thereof; [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans- (S,S)-cyclohexane-1,2-diamine-pentaacetic acid (p-SCN-Bn-CHX-A”-DTPA) or a derivative thereof; TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) or a derivative thereof; SarAr (1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8- diamine or a derivative thereof; NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) or a derivative thereof; NETA (4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl- [1,4,7]triazonan-1-yl) acetic acid or a derivative thereof; TRAP (1,4,7-triazacyclononane-1,4,7- tris[methyl(2-carboxyethyl)phosphinic acid) or a derivative thereof; HBED (N,N0-bis(2- hydroxybenzyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; 2,3-HOPO (3- hydroxypyridin-2-one) or a derivative thereof; PCTA (3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca- 1(15),11,13-triene-3,6,9,-triacetic acid) or a derivative thereof; DFO (desferrioxamine) or a derivative thereof; DTPA (diethylenetriaminepentaacetic acid) or a derivative thereof; OCTAPA (N,N0-bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; H2-MACROPA (N,N'-bis[(6-carboxy-2-pyridipmethyl]-4,13-diaza-18-crown-6) or a derivative thereof; H2dedpa (1,2-[[carboxy)-pyridin-2-yl]-methylamino]ethane or a derivative thereof; and EC20-head comprising β-l-diaminopropionic acid, aspartic acid, and cysteine, wherein the chelating group optionally chelates a metal. B, B’ and B” can independently comprise a radioisotope / radionuclide for radio-imaging, radiotherapy, or magnetic resonance imaging (MRI). The radioisotope / radionuclide can be selected from the group consisting of177Lu,90Y,211At,225Ac,161Tb,18F,32P,44Sc,47Sc,52Mn,55Co,64Cu,67Cu,67Ga,68Ga,86Y,89Sr,89Zr,99mTc,111In,114mIn,117mSn,124I,125I,131I,149Tb,153Sm,152Tb,155Tb,169Er,186Re,188Re,212Pb,212Bi,213Bi,223Ra,224Ra,225Ac,161Tb, and227Th. The radioisotope / radionuclide can be selected from the group consisting of11C,13C,13N,15O,60Co, and123I. B, B’ and B”, independently, can be or can comprise:

[0021] wherein each X is independently a radioisotope selected from the group consisting of 18p,124I,125I,131I, and2llAt; each R and R' is independently selected from -H, -D, -C1-C3 alkyl, benzyls, and substituted benzyls; and each n is independently an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. B can be or can comprise a radiolabeled prosthetic group selected from the group consisting of: B, B’ and B” can independently comprise a chelating agent selected from:

[0022] B, B’ and B” can independently comprise a nuclide for positron emission tomography (PET) or single-photon emission computed tomography (SPECT). The nuclide can be selected from the group consisting of99mTc,111In,18F,68Ga,124I,125I,131I, and64Cu. B can be an anti- tumor agent selected from: .

[0023] inhibitor (e.g., camptothecin, topotecan), an hypoxia-activated anthraquinone (e.g., AQ4N), and an alkylating agents (e.g., temozolomide). B, B’ and B” can independently be an DNA repair inhibitor (e.g., poly (ADP ribose) polymerase inhibitors (AG14,361, Fuzuloparib, Olaparib, Pamiparib (BGB-290), and Rucaparib) or a PRMT5 inhibitor (e.g., JNJ-64619178) or DNA-PKc inhibitors (AZD7648, Peposertib (M3814) or ATM inhibitors (AZD0156, AZD1390) or dual DNA-PKc and ATM inhibitor (XRD-0394). B can comprise a chemotherapeutic agent. The chemotherapeutic agent can be a Wnt / ^-catenin inhibitor. The chemotherapeutic / anti-fibrotic agent can be a kinase inhibitor for vascular endothelial growth factor receptor (VEGFR), such as an inhibitor for VEGFR1, VEGFR2, or VEGFR3, fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), a platelet-derived growth factor receptor (PDGFR), a phosphatidylinositol-3-kinase (PI3k) inhibitor, a dual inhibitor of the PI3k / mTOR signaling pathway, or a transforming growth factor β (TGFβ) inhibitor. See, for example, Fig.101. The agent may also be a dual inhibitor of the PI3k / mTOR signaling pathway, the dual inhibitor can be:

[0024] from the group consisting of: In an . can have the structure. N N X O A Z -CO-, The TGFβ inhibitor can have the structure: . have the structure: O N . The ROCK inhibitor can have the structure: . . The chemotherapeutic / anti-fibrotic agent can be an inhibitor of focal adhesion kinase (FAK) or an inhibitor of Rho-associated protein kinase (ROCK). The chemotherapeutic agent can be a fibroblast killing agent. The fibroblast killing agent can be an anti-mitotic agent (e.g., DM1 or DM4), an auristatin (e.g., MMAE or MMAF), a DNA methylation agent, or an apoptosis inducer. The chemotherapeutic agent can be a fibroblast inactivating agent. The fibroblast inactivating agent can be an antifibrotic agent. The chemotherapeutic agent can be a fibroblast proliferating agent, a fibroblast suppressing agent, an activator of fibroblast differentiation, or an inhibitor of fibroblast differentiation. The chemotherapeutic agent can be an inhibitor of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). The chemotherapeutic agent can be an agonist of a toll-like receptor. B, B’, and B’’ can independently comprise a structure selected from:

[0025] O OHOH N O H NaO S SO NaO S SO . C can be an albumin binding ligand, a plasma protein binder, a hapten, a disulfide- stabilized protein scaffold comprising albumin binding domain 035 (ABD035), albumin binding domain Con (i.e., a peptide of a three-helix bundle 45 amino acids in length (ABDCon)), a designed ankyrin repeat protein (DARPin), a disulfide-stabilized Fv fragment (dsFv) of an anti- albumin antibody (e.g., CA645), a nanobody that complexes with human serum albumin (HSA), or a variable new antigen receptor (VNAR) (e.g., E06). C can be or can comprise:

[0026] NH

[0027] wherein, as applicable, each of R12-19 (where applicable) is independently selected from -H, -C1- C6alkyl, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, -C(O)alkyl, -C(O)aryl-, -C=C-C(O)aryl, -C=C-S(O)2aryl, -CO2H, -SO3H, -SO2NH2, -PO3H2, and -SO2F; and each of R20 and R21 is independently selected from -H, -C1-C6 alkyl, -F, -Cl, -Br, -I, -O-C1-6 alkyl, -CN, -CHO, - B(OH)2, -C=C-C(O)aryl, -C=C-S(O)2aryl, -CO2H, -SO3H, -SO2NH2, -PO3H2, -SO2F, CF3, and O .

[0028] . (e.g., a radical of) (PEG)n, wherein n is an integer 0 to 32, a peptide, a peptidoglycan, or a saccharide. C can comprise: . C can be a hapten bound an α-galactosyl moiety, a dinitrophenyl (DNP) moiety, and a trinitrophenyl (TNP) moiety. The conjugate of formula (I) can have the following structure:

[0029] F FO OMe F FO OMeN N H OMe N H N H OMe N O H The conjugate of formula (I) can have the following structure:

[0030] r wherein n is an integer fro . The conjugate of formula (I) can have the following structure:

[0031] The conjugate of formula (I) can have the following structure:

[0032] herapy, or MRI. The conjugate of formula (I) can have the following structure:

[0033] MRI. The conjugate of formula (I) can have the following structure:

[0034] wherei py, or MRI. The conjugate of formula (II) can have the following structure:

[0035] wherein the structure is optionally bound to a metal suitable for radio-imaging, radiotherapy, or MRI. The conjugate of formula (II) can have the following structure: HO O HO O S I O SO H O H HO O OH NH N N N OH or MRI. The conjugate of formula (II) can have the following structure: .

[0036] wherein the structure is optionally bound to a metal suitable for radio-imaging, radiotherapy, or MRI. The conjugate of formula (II) can have the following structure: MRI. The conjugate of formula (II) can have the following structure:

[0037] , or MRI. The conjugate of formula (II) can have the following structure: MRI. The conjugate of formula (II) can have the following structure:

[0038] apy, or MRI. The conjugate of formula (II) can have the following structure: or MRI. The conjugate of formula (II) can have the following structure: O O OOHO H N H O . .

[0039] . .

[0040] . ucture: .

[0041] . .

[0042] .

[0043] . . . The conjugates can contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that are defined, in terms of absolute stereochemistry, as (R)- or (S)-. Unless stated otherwise, it is intended that all stereoisomeric forms of the conjugates are contemplated. When the conjugates described herein contain alkene double bonds, and unless specified otherwise, it is intended that this disclosure includes both E and Z geometric isomers (e.g., cis or trans). Likewise, all possible isomers, as well as their racemic and optically pure forms, and all tautomeric forms are also intended to be included. The term “geometric isomer” refers to E or Z geometric isomers (e.g., cis or trans) of an alkene double bond. The term “positional isomer” refers to structural isomers around a central ring, such as ortho-, meta-, and para- isomers around a benzene ring. Further, it is understood that replacement of one or more hydrogen atoms with deuterium can significantly lower the rate of metabolism of a drug and, therefore, increase its half-life. The moiety S0456 has the structure a salt thereof. In The moiety OTL38 (also known as “Cytalux”) has the structure

[0044] , or a salt thereof. In some embodiments, In so , ed microphages (TAMs) in the microenvironment. The term “universal cocktail mixture” refers to a combination of FAP9-S0456 and OTL38. In some embodiments, an additional conjugate may be included in the mixture. In certain embodiments, the additional conjugate can be a carbonic anhydrase nine (CA-IX) targeting ligand. One CA-IX ligand has the structure SO3H SO3H one or more hydrogen atoms contained therein are replaced by one or more non-hydrogen atoms. The term “functional group” or “substituent” as used herein refers to a group that can be or is substituted onto a molecule. Examples of substituents or functional groups include, but are not limited to, a halogen (e.g., F, Cl, Br, and I); an oxygen atom in groups such as hydroxyl groups, alkoxy groups, aryloxy groups, aralkyloxy groups, oxo(carbonyl) groups, carboxyl groups including carboxylic acids, carboxylates, and carboxylate esters; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfoxide groups, sulfone groups, sulfonyl groups, and sulfonamide groups; a nitrogen atom in groups such as amines, azides, hydroxylamines, cyano, nitro groups, N-oxides, hydrazides, and enamines; and other heteroatoms in various other groups. The term “optionally substituted,” or “optional substituents,” as used herein, means that the groups in question are either unsubstituted or substituted with one or more of the substituents specified. When the groups in question are substituted with more than one substituent, the substituents may be the same or different. When using the terms “independently,” “independently are,” and “independently selected from” mean that the groups in question may be the same or different. Certain of the herein defined terms may occur more than once in the structure, and upon such occurrence each term shall be defined independently of the other. "Oxo" refers to the =O radical. "Alkyl" generally refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, such as having from one to fifteen carbon atoms (e.g., C1- C15 alkyl). "Alkyl" is intended to include independent recitations of a saturated "alkyl, " unless otherwise stated. An alkyl can comprise one to thirteen carbon atoms (e.g., C1-C13 alkyl). An alkyl can comprise one to eight carbon atoms (e.g., C1-C8alkyl). An alkyl can comprise one to five carbon atoms (e.g., C1-C5alkyl). An alkyl can comprise one to four carbon atoms (e.g., C1- C4 alkyl). An alkyl can comprise one to three carbon atoms (e.g., C1-C3 alkyl). An alkyl can comprise one to two carbon atoms (e.g., C1-C2alkyl). An alkyl can comprise one carbon atom (e.g., C1alkyl). An alkyl can comprise five to fifteen carbon atoms (e.g., C5-C15alkyl). An alkyl can comprise five to eight carbon atoms (e.g., C5-C8 alkyl). An alkyl can comprise two to five carbon atoms (e.g., C2-C5alkyl). An alkyl can comprise three to five carbon atoms (e.g., C3-C5alkyl). In various embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n- propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2- methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond. "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above. "Alkylene" or "alkylene chain" generally refers to a straight or branched divalent alkyl group linking the rest of the molecule to a radical group, such as having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, i-propylene, n-butylene, and the like. "Aryl" refers to a radical derived from an aromatic monocyclic or multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or multicyclic hydrocarbon ring system contains only hydrogen and from five to eighteen carbon atoms, where at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The ring systems from which aryl groups are derived include, but are not limited to, benzene, fluorene, indane, indene, tetralin and naphthalene. "Aralkyl" or "aryl-alkyl" refers to a radical of the formula -Rc-aryl, where Rcis an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. "Carbocyclyl" or "cycloalkyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, having from three to fifteen carbon atoms. A carbocyclyl can comprise three to ten carbon atoms. A carbocyclyl can comprise five to seven carbon atoms. The carbocyclyl is attached to the rest of the molecule by a single bond. Carbocyclyl or cycloalkyl is saturated (i.e., containing single C-C bonds only) or unsaturated (i.e., containing one or more double bonds or triple bonds). Examples of saturated cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. An unsaturated carbocyclyl is also referred to as "cycloalkenyl." Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic carbocyclyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. "Carbocyclylalkyl" refers to a radical of the formula –Rc-carbocyclyl, where Rcis an alkylene chain as defined above. "Halo" or "halogen" refers to a bromo, chloro, fluoro or iodo substituent. "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halogen radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. The term "heteroalkyl" refers to an alkyl group as defined above in which one or more skeletal carbon atoms of the alkyl are substituted with a heteroatom (with the appropriate number of substituents or valencies – for example, -CH2- may be replaced with -NH- or -O-). For example, each substituted carbon atom is independently substituted with a heteroatom, such as wherein the carbon is substituted with a nitrogen, oxygen, selenium, or other suitable heteroatom. In some instances, each substituted carbon atom is independently substituted for an oxygen, nitrogen (e.g. -NH-, -N(alkyl)-, or -N(aryl)- or having another substituent contemplated herein), or sulfur (e.g. -S-, -S(=O)-, or -S(=O)2-). A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. A heteroalkyl is attached to the rest of the molecule at a heteroatom of the heteroalkyl. A heteroalkyl is a C1-C18heteroalkyl. A heteroalkyl is a C1-C12 heteroalkyl. A heteroalkyl is a C1-C6 heteroalkyl. A heteroalkyl is a C1- C4 heteroalkyl. Heteroalkyl can include alkoxy, alkoxyalkyl, alkylamino, alkylaminoalkyl, aminoalkyl, heterocycloalkyl, heterocycloalkyl, and heterocycloalkylalkyl, as defined herein. "Heteroalkylene" refers to a divalent heteroalkyl group defined above which links one part of the molecule to another part of the molecule. "Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic ring radical that can comprise two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which optionally includes aromatic, fused, and / or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. The heterocyclyl radical is partially or fully saturated. "Heterocyclyl" is intended to include independent recitations of heterocyclyl comprising aromatic and non- aromatic ring structures, unless otherwise stated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, 1,3-benzodioxolyl, 1,4-benzodioxanyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, indolinyl, isoindolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. "N-heterocyclyl" or "N-attached heterocyclyl" refers to a heterocyclyl radical as defined above containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. Examples of such N-heterocyclyl radicals include, but are not limited to, 1-morpholinyl, 1- piperidinyl, 1-piperazinyl, 1-pyrrolidinyl, pyrazolidinyl, imidazolinyl, and imidazolidinyl. "Heteroaryl" refers to a radical derived from a 3- to 18-membered aromatic ring radical that can comprise two to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. The heteroaryl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical is optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pridinyl, and thiophenyl (i.e. thienyl). The compounds and conjugates can be presented as a pharmaceutically acceptable salt. The term “pharmaceutically acceptable salt” refers to those salts whose counter ions can be used in pharmaceuticals. In various embodiments, such salts include, but are not limited to 1) acid addition salts, which can be obtained by reaction of the free base of the parent compound with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, and perchloric acid and the like, or with organic acids such as acetic acid, oxalic acid, (D) or (L) malic acid, maleic acid, methane sulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, salicylic acid, tartaric acid, citric acid, succinic acid or malonic acid and the like; or 2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, trimethamine, N- methylglucamine, and the like. Pharmaceutically acceptable salts are well-known to those skilled in the art, and any such pharmaceutically acceptable salt is contemplated in connection with the embodiments described herein. Pharmaceutically acceptable salts can be synthesized from the parent conjugate / compound which contains a basic or acidic moiety by conventional chemical methods. In some instances, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington’s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, the disclosure of which is hereby incorporated by reference. In certain embodiments, it can be desired to modify the conjugate and / or composition synthesis process to optimize yield at production (e.g., when the conjugate is optionally bound to a metal suitable for radio-imaging, radiotherapy, or magnetic resonance imaging). For example, a multiple step process can be utilized to facilitate stability of the conjugate at the pH required for radiolabeling. In various embodiments, suitable acid addition salts are formed from acids which form non-toxic salts. Illustrative examples include the acetate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulphate / sulphate, borate, camsylate, citrate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulphate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate and trifluoroacetate salts. In various embodiments, suitable base salts are formed from bases which form non-toxic salts. Illustrative examples include the arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts. Hemisalts of acids and bases also can be formed, for example, hemisulphate and hemicalcium salts. In each embodiment hereof, it will be understood that the formulae include and represent not only all pharmaceutically acceptable salts of the compounds and conjugates, but also include any and all hydrates of the compound formulae or salts thereof where appropriate. The term “solvate” means a compound, or a salt thereof, that further includes a stoichiometric or non- stoichiometric amount of solvent bound by non-covalent intermolecular forces. Where the solvent is water, the solvate is a “hydrate.” Certain functional groups, such as the hydroxy, amino, and like, can form complexes and / or coordination conjugates with water and / or various solvents. Accordingly, the formulae are to be understood to include and represent those various hydrates and / or solvates. Non-hydrates and / or non-solvates of the compounds and conjugates are also included. The ligands and conjugates can be synthesized in accordance with methods known in the art and exemplified herein. Also provided is a pharmaceutical composition comprising an above-described conjugate and a pharmaceutically acceptable carrier. The term "composition" generally refers to any product comprising more than one ingredient, including the conjugate. The compositions can be prepared from isolated conjugates or from salts, solutions, hydrates, solvates, and other forms of the conjugates. The term “pharmaceutically acceptable carrier” means one or more compatible solid or liquid fillers, diluents or encapsulating substances which are suitable for administration to a human or other vertebrate animal. The term “carrier” denotes an organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate the application. The carrier can be an excipient. The choice of carrier can depend on factors such as the particular mode of administration, the effect of the carrier on solubility and stability, and the nature of the dosage form. For example, the carrier can be suitable for parenteral administration. Pharmaceutical compositions suitable for the delivery of compounds as described herein and methods for their preparation may be found, for example, in Remington: The Science & Practice of Pharmacy, 21st edition (Lippincott Williams & Wilkins, 2005). Pharmaceutically acceptable carriers can include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. Examples of such carriers (or excipients) include, but are not limited to, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. Liquids within which the conjugate can be dispersed include a carrier liquid or an in vivo liquid. By the conjugate being "dispersed" throughout or in a liquid is meant that the conjugate presents as a dispersed phase within the liquid which itself, relative to the conjugate, presents as a continuous liquid medium or phase. The term "liquid" in the context of a liquid carrier is intended to mean a vehicle in which the conjugate is dispersed and which is in a liquid state at least at the temperature of intended use. A liquid carrier can be made up of one or more different liquids. Suitable pharmacologically acceptable liquid carriers are described in Martin, Remington's Pharmaceutical Sciences, 18thEd., Mack Publishing Co., Easton, PA, (1990), and include, but are not limited to, liquids that are sterilized, such as water and oils, including those of petroleum, animal, vegetable, mineral or synthetic origin, such as peanut oil, soya bean oil, mineral oil, sesame oil, and the like. Other liquid carriers include methylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, ethanol, isopropyl alcohol, and benzyl alcohol. Water or soluble saline solutions and aqueous dextrose and glycerol solutions can be employed as liquid carriers, particularly for injectable solutions. In practice, the conjugate can be taken up by a subject in vivo, for example, when the conjugate is administered orally or parenterally. In that case, a liquid carrier originally carrying the conjugate can become so dilute in vivo that the surrounding liquid environment throughout which the conjugate is dispersed becomes more representative of an in vivo liquid (i.e., a biological liquid / fluid within the subject) than the original liquid carrier. For example, once administered parenterally, the conjugate might more aptly be described as being dispersed throughout blood rather than an original liquid carrier. Under those circumstances, it can be convenient to refer to the conjugate as being dispersed throughout an in vivo liquid carrier (i.e., a biological liquid / fluid within the subject). The components of the compositions also can be commingled with the conjugate, and with each other, in a manner such that there is no interaction which would substantially impair the desired pharmaceutical efficiency. The composition can comprise cremophor, polysorbate, nanoparticles, a polymer, or a hydrogel, for example. In certain embodiments, the pharmaceutical composition comprises a plurality of conjugates and a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier can include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, and combinations thereof, that are physiologically compatible. One or more other active agents also can be incorporated into a pharmaceutical composition. In certain embodiments, a pharmaceutical composition further comprises at least one additional pharmaceutically active agent. The at least one additional pharmaceutically active agent can be an agent useful in the treatment of a cancer. In certain embodiments, the at least one additional pharmaceutically active agent can be an agent useful for radiotherapy. In certain embodiments, the at least one additional pharmaceutically active agent can be an agent useful for imaging (e.g., diagnostic imaging). Pharmaceutical compositions can be prepared by combining one or more conjugates with a pharmaceutically acceptable carrier and, optionally, one or more additional ingredients (e.g., pharmaceutically active ingredients). The formulations can be administered in pharmaceutically acceptable solutions, which can routinely contain pharmaceutically acceptable concentrations of salt, buffering agents, preservatives, compatible carriers, adjuvants, and optionally other therapeutic ingredients. Compositions can comprise one or more pharmacologically acceptable additives known to those in the art. For example, the liquid carrier may comprise one or more additives such as wetting agents, de-foaming agents, surfactants, buffers, electrolytes, preservatives, colourings, flavourings, and sweeteners. The particular nature of a liquid carrier and any additive (if present) can, in part, depend upon the intended application of the composition. A suitable liquid carrier and additive (if present) can be selected for the intended application of the composition. The composition is suitable for administration to a subject for diagnostic, mapping, and / or therapeutic applications. By "suitable" for administration is meant that administration of the conjugate / composition to a subject will not result in unacceptable toxicity, including allergenic responses and disease states. For use in therapy or treatment, an effective amount of the conjugate or composition can be administered to a subject by any mode that delivers the conjugate(s) as desired. Administering a composition can be accomplished by any means known to the skilled artisan. Routes of administration include, but are not limited to, intravenous, intramuscular, intraperitoneal, intravesical (urinary bladder), oral, subcutaneous, direct injection, mucosal (e.g., topical to eye), inhalation, and topical. Colorants and / or flavoring agents can be included. For example, the conjugate can be formulated (such as by liposome or microsphere encapsulation) and then further contained within an edible product, such as a refrigerated beverage containing colorants and flavoring agents. Illustrative formats for oral administration include, but are not limited to, tablets, capsules, elixirs, syrups, and the like. In certain embodiments, a conjugate and / or composition can be administered directly into the blood stream, into muscle, or into an internal organ. Suitable routes for such parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular, intranasal, and subcutaneous. Suitable means for parenteral administration include needle (including microneedle) injectors, needle-free injectors, and infusion techniques. Where it is desirable to deliver the compound(s) and / or compositions systemically, the compound(s) and / or composition can be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection can be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions can take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and can contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Parenteral formulations are typically aqueous or non-aqueous isotonic sterile solutions that can contain carriers or excipients, such as salts, carbohydrates, anti-oxidants, bactericide, solute and / or buffering agents (preferably at a pH of 3–9) which renders the composition isotonic with the blood of the intended subject, but, for some applications, they may be more suitably formulated as a sterile non-aqueous solution or as a dried form to be used in conjunction with a suitable vehicle, such as sterile, pyrogen-free water. Such compositions can be presented in unit- dose or multi-dose sealed containers, for example, ampoules and vials. A liquid formulation can be adapted for parenteral administration of a conjugate or composition as described herein. The preparation of parenteral formulations under sterile conditions, for example, by lyophilization under sterile conditions, can readily be accomplished using standard pharmaceutical techniques well-known to those skilled in the art. The solubility of a conjugate can be increased by the use of appropriate formulation techniques, such as the incorporation of solubility-enhancing agents. Formulations for parenteral administration can be formulated for immediate and / or modified release. A conjugate can be administered in a time-release formulation, for example in a composition which includes a slow-release polymer. The conjugate can be prepared with a carrier that will protect it against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid and polylactic, polyglycolic copolymers (PGLA). Methods for the preparation of such formulations are generally known to those skilled in the art. Sterile injectable solutions can be prepared by incorporating the conjugate(s), alone or in further combination with one or more other active agents, in the required amount in an appropriate solvent with one or a combination of ingredients described above, as required, followed by filtered sterilization. Typically, dispersions are prepared by incorporating the conjugate(s) into a sterile vehicle, which contains a dispersion medium and any additional ingredients of those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying, which yield a powder of the active ingredients plus any additional desired ingredient from a previously sterile-filtered solution thereof, or the ingredients can be sterile-filtered together. The pharmaceutical composition can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable to high drug concentration. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion, and by the use of surfactants. A conjugate, or a pharmaceutical composition comprising a conjugate, can be continuously administered, where appropriate. Further provided is a method of imaging cancer or fibrosis in a patient. The method comprises administering to the patent an above-described conjugate, or a pharmaceutical composition comprising same, and imaging the cancer or the fibrosis in the patient. Still further provided is a method of treating cancer or inflammation in a patient. The method comprises administering to the patient an effective amount of an above-described conjugate, or a pharmaceutical composition comprising same, whereupon the patient is treated for cancer, fibrosis or inflammation. As used herein, "subject" means either an animal or human subject. "Animal" means primates, livestock animals (including, without limitation, cows, horses, sheep, pigs and goats), companion animals (including dogs, cats, rabbits and guinea pigs), and captive wild animals (including those commonly found in a zoo environment). Laboratory animals such as rabbits, mice, rats, guinea pigs and hamsters are also contemplated as they may provide a convenient test system. Given that FAP homologs have been found in zebrafish and amphibians, i.e., two species of the Xenopus genus, the subject, in certain instances, could be a fish or an amphibian. The subject can be a human or a mammal of economic importance and / or social importance to humans, for instance, carnivores other than humans (e.g., cats and dogs), swine (e.g., pigs, hogs, and wild boars), ruminants (e.g., cattle, oxen, sheep, giraffes, deer, goats, bison, and camels), horses, and birds including those kinds of birds that are endangered and kept in zoos, and fowl, more particularly domesticated fowl (e.g., poultry, such as turkeys, chickens, ducks, geese, guinea fowl, and the like) as they are also of economic importance to humans. The term "subject" does not denote a particular age. Thus, adult, juvenile and newborn subjects are covered. The terms "subject, " "individual" and "patient" may be used interchangeably herein. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the method of imaging FAP+ cells in a subject comprises (i) administering to the subject one or more conjugates described herein or pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition comprising the same and (ii) obtaining an image of the conjugate(s) (or a portion thereof) bound to FAP on the surfaces of cells displaying FAP, whereupon FAP+ cells in the subject are imaged. In certain embodiments, a method of imaging FAP+ cells in a subject comprises (i) administering to the subject one or more conjugates described herein or pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition comprising the same and (ii) imaging the conjugate(s) or stereoisomer or pharmaceutically acceptable salt, hydrate, or solvate thereof (or a portion thereof) bound to FAP on the surfaces of cells displaying FAP. The conjugate(s), or pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition employed in the methods hereof can be any of the conjugates, pharmaceutically acceptable salts, hydrates or solvates thereof, or pharmaceutical compositions described herein. In certain embodiments, the conjugate administered to the subject pursuant to the method of imaging is a conjugate of formula I or II. In certain embodiments, the imaging is performed after administering the conjugate(s), or pharmaceutically acceptable salt, hydrate or solvate thereof, or pharmaceutical composition. The imaging can be performed by magnetic resonance imaging (MRI), ultrasound, X-ray, optical imaging, Computed Tomography (CT), Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET), Fluorescence Resonance Energy Transfer (FRET), or any combination of two or more of the foregoing. Accordingly, the conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, and / or composition can be used in conjunction with other in vivo imaging techniques including, but not limited to, ultrasound, X- ray, optical imaging, CT, SPECT, PET and FRET. The method can further comprise the simultaneous or sequential administration, in either order, of an effective amount of an active agent that is a free radiosensitizer, radioprotector, immunotherapeutic agent, chemotherapeutic agent, anti-cancer drug, or hormone therapeutic agent, or a pharmaceutical composition (e.g., the second pharmaceutical composition) comprising same and a pharmaceutically acceptable carrier or excipient. In certain embodiments, the active agent comprises a radioprotectant. In certain embodiments, the radioprotectant active agent comprises Lys. The subject can have cancer and the cells, the tissue, or the organ with cancer can be imaged, whereupon cancer is detected. The subject can have a tumor with a microenvironment, and the method can further comprise obtaining a map of the microenvironment of the tumor. The subject can have a tumor, and the method can further comprise obtaining a measurement of a gross target volume and / or a clinical target volume for treatment. As used herein, the expression "tumor microenvironment" refers to a heterogeneous population of non-cancerous cells surrounding and / or infiltrating a tumor, which are essential to the functionality, physiology and metastasis of the tumor. The skilled person will appreciate that the tumor microenvironment comprises a range of different cell types that may differ based on the size, location, type and stage of a tumor, illustrative examples of which include fibroblasts, pericytes, adipocytes, mesenchymal stromal cells (MSCs), cancer cells and endothelial cells, and combinations thereof (such as pericytes and endothelial cells). While the cells of the tumor microenvironment can be non-cancerous, tumors can recruit and / or regulate such cells to provide a favorable environment to facilitate cancer growth. Accordingly, cells comprised within the tumor microenvironment may be referred to as "cancer-associated" or "tumor-associated." As the conjugates and compositions hereof can be used to label the cancer cells (by binding, for example, FAP8), the methods hereof can be used to visualize, characterize, monitor and facilitate treatment of a cancer or other disease. When the subject has been treated for cancer and the tumor site (e.g., tumor microenvironment) in the subject is imaged, the method can further comprise assessing or monitoring the efficacy of treatment. For example, the conjugates and / or compositions can be used to monitor tumor or lesion growth and proliferation quantitatively in vivo. In certain embodiments, a method of monitoring a progression of a cancer in a subject is provided, comprising administering a conjugate, a pharmaceutically acceptable salt, solvate, hydrate, or stereoisomer thereof, or a pharmaceutical composition comprising the conjugate or a pharmaceutically acceptable salt, solvate, hydrate, or stereoisomer thereof to a subject. Such method can further comprise imaging the cancer of the subject. The subject can be imaged periodically over the course of a therapeutic treatment, and a practitioner can then compare the images and / or otherwise quantify lesion or cancer growth to determine therapeutic efficacy (e.g., if there is a differential killing effect of the cancer cells over the course of the therapeutic treatment, or a relative increase in lesion size or cancer growth). Accordingly, a method is provided for determining a likelihood of success of a therapeutic treatment in a subject. In certain embodiments, the method further comprises assessing or monitoring efficacy of a treatment administered to the subject. Therapeutic and diagnostic applications suitable for treatment of a condition experienced by the subject can also be employed in combination with the imaging method hereof. Non- limiting examples of suitable therapeutic or diagnostic applications include MRI, MRI guided external beam radiotherapy, MRI guided focal ablation, MRI / Ultrasound fusion focal ablation, MRI guided biopsy, MRI / Ultrasound fusion guided biopsy, MRI guided surgery, MRI guided brachytherapy, and MRI guided infrared camera guided biopsy or therapy. In certain embodiments, the method further comprises administering radiotherapy to the subject, wherein the radiotherapy is administered before, concurrent with, or sequential to administering the conjugate, stereoisomer or a pharmaceutically acceptable salt, hydrate, or solvate of the conjugate, or the composition to the subject. As noted above, the conjugate / composition comprising one or more conjugates can allow for the detection of cells expressing FAP, such as cells within the tumor microenvironment (e.g., tumor-associated stromal cells and cancer cells) associated with solid tumors. The solid tumors and / or cancer can comprise prostate cancer, glioblastoma, pancreatic cancer, colorectal cancer, breast cancer and lung cancer, for example. By specifically binding to FAP expressed by the cells of the tumor microenvironment, the conjugate can be useful for the identification of the boundaries and margins of tissue affected by cancer (i.e., tumor mapping). It is also contemplated herein that the conjugate(s) and compositions can be useful for the detection (i.e., diagnosis) of cancer or as part of the treatment of cancer. For example, the conjugate(s), pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or compositions can be used for tumor mapping. In certain embodiments, tumor mapping is performed prior to the commencement of treatment, such as focal therapy, radiotherapy, proton therapy or brachytherapy. Furthermore, by accurately mapping a tumor, including regions of the tumor microenvironment, surgical resection of the tumor can be performed with more accuracy to limit undesirable side effects and minimizing the risk of suboptimal debulking of the tumor mass. When the conjugates, pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or pharmaceutical compositions comprising the conjugate(s) are administered for imaging, i.e., MRI, the conjugate(s) pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or compositions can be administered by any suitable route including, for example, intravenously, intraperitoneally, subcutaneously, intracranially, intradermally, intramuscularly, intraocularly, intrathecally, intracerebrally, and intranasally. Typically, the conjugate(s), pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or compositions are administered intravenously or orally. The conjugates and compositions are administered orally for gastrointestinal scans. The conjugate(s), pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or compositions comprising them can be administered intratumorally or peritumorally. The amount of conjugate(s), pharmaceutically acceptable salts, hydrates, or solvates thereof, and / or compositions administered can, in certain embodiments, be the smallest amount sufficient to generate a clinically useful image. Amounts of currently available contrast agents can be used as a guide in determining the amounts of the conjugate(s), pharmaceutically acceptable salts or hydrates thereof, and / or compositions to be used. In certain embodiment, the methods hereof further comprise treating the subject, or having the subject treated, for cancer. For example, the method can further comprise administering an effective amount of a treatment for cancer (e.g., a second anti-cancer therapy) at a site where the conjugate accumulates. The treatment can be any suitable treatment, such as surgery, radiotherapy, brachytherapy, photodynamic therapy, photothermal therapy, focal ablation therapy including cryoablation, focal laser ablation and high-frequency ultrasound ablation, chemotherapy, and immunotherapy. As for treatment, the therapeutic regimen for the treatment of a disease state (e.g., cancer, an inflammatory disease or disorder, etc.) can be determined by a person skilled in the art and will typically depend on factors including, but not limited to, the type, size, stage and receptor status of a tumor (e.g., with cancer) in addition to the age, weight and general health of the subject. Another determinative factor can be the risk of developing recurrent disease. For instance, for a subject identified as being at high risk or higher risk or developing recurrent disease, a more aggressive therapeutic regimen can be prescribed as compared to a subject who is deemed at a low or lower risk of developing recurrent disease. Similarly, for a subject identified as having a more advanced stage of cancer, for example, stage III or IV disease, a more aggressive therapeutic regimen can be prescribed as compared to a subject that has a less advanced stage of cancer. The terms "treat," "treatment," and "treating" refer to any and all uses which remedy a condition or symptom, or otherwise prevent, hinder, retard, abrogate or reverse the onset or progression of cancer or other undesirable symptoms in any way whatsoever. Thus, the term "treating," and the like, is to be considered in its broadest possible context. For example, treatment does not necessarily imply that a subject is treated until total recovery or cure. In conditions that display or are characterized by multiple signs or symptoms, the treatment need not necessarily remedy, prevent, hinder, retard, abrogate or reverse all signs or symptoms, but can remedy, prevent, hinder, retard, abrogate or reverse one or more signs or symptoms. The expression "therapeutically effective amount" means the amount of conjugate when administered to a mammal, in particular a human, in need of such treatment, is sufficient to treat cancer. The precise amount of conjugate to be administered can be determined by a physician with consideration of individual differences in age, weight, tumor size, extent of infection or metastasis, and condition of the subject. "Administration" of the conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, and / or composition to a subject is meant that the conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, or composition is presented such that the conjugate(s) and / or pharmaceutically acceptable salts, hydrates, or solvates thereof can be transferred to the subject. There is no particular limitation on the mode of administration, but this will generally be by way of oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous, intracerebrally, intranasally, intrathecal, and intraspinal), inhalation (including nebulization), topical, rectal and vaginal modes. The conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, and / or composition can also be administered directly into a tumor and / or into tissue adjacent one or more segments of a tumor or administered directly into blood vessels. The conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, and / or composition can be administered in, as appropriate, a treatment or diagnostic effective amount. A treatment or diagnostic effective amount includes an amount which, when administered according to the desired dosing regimen, achieves a desired therapeutic or diagnostic effect, including one or more of: alleviating the symptoms of, preventing or delaying the onset of, inhibiting or slowing the progression of, diagnosing, or halting or reversing altogether the onset or progression of a particular condition being treated and / or assessed. As used herein, “effective amount” means and encompasses both therapeutically effective amount and treatment or diagnostic effective amount. Suitable dosage amounts and dosing regimens to achieve this can be determined by the attending physician and can depend on the particular condition being treated or diagnosed, the severity of the condition as well the general age, health and weight of the subject. Depending upon the route of administration, a wide range of permissible dosages are contemplated. The dosing can occur at intervals of minutes, hours, days, weeks, months or years or continuously over any one of these periods. Suitable dosages of the particulate material per se can lie within the range of about 0.1 ng per kg of body weight to 1 g per kg of body weight per dosage. The dosage can be in the range of 1 µg to 1 g per kg of body weight per dosage, such as is in the range of 1 mg to 1 g per kg of body weight per dosage. In one embodiment, the dosage can be in the range of 1 mg to 500 mg per kg of body weight per dosage. In another embodiment, the dosage can be in the range of 1 mg to 250 mg per kg of body weight per dosage. In yet another embodiment, the dosage can be in the range of 1 mg to 100 mg per kg of body weight per dosage, such as up to 50 mg per body weight per dosage. Conjugate(s), pharmaceutically acceptable salt, hydrate, or solvate thereof, and / or compositions hereof can be administered in a single dose or a series of doses. For example, dosages may be single or divided and may be administered according to a wide variety of protocols, including q.d. (once a day), b.i.d. (twice a day), t.i.d. (three times a day), or even every other day, once a week, once a month, once a quarter, and the like. In each of these cases it is understood that the effective amounts described herein correspond to the instance of administration, or alternatively to the total daily, weekly, month, or quarterly dose, as determined by the dosing protocol. In addition to the illustrative dosages and dosing protocols described herein, an effective amount of any one or a mixture of the compounds described herein can be determined by the attending diagnostician or physician by the use of known techniques and / or by observing results obtained under analogous circumstances. In determining the effective amount or dose, a number of factors are considered by the attending diagnostician or physician, including, but not limited to the species of mammal, including human, its size, age, and general health, the specific disease or disorder involved, the degree of or involvement or the severity of the disease or disorder, the response of the individual patient, the particular compound administered, the mode of administration, the bioavailability characteristics of the preparation administered, the dose regimen selected, the use of concomitant medication, and other relevant circumstances. In certain embodiments, a use of a conjugate, a pharmaceutically acceptable salt, hydrate, or solvate of the conjugate, or a composition hereof in the manufacture of a medicament for the treatment of a disease in a subject is provided. The conjugate can be any compound or conjugate hereof. The disease in the subject can be cancer. The disease in the subject can be an inflammatory disease or disorder. Any of the conjugates and / or compositions hereof can be for use in the treatment of a subject experiencing and / or having a disease state described herein. The disease state, for example, can be cancer or an inflammatory disease or disorder. Some embodiments concern methods of imaging cancer or fibrosis in a patient, which method comprises (i) administering to the patent a combination of NIR imaging agents comprising (ii) cancer or the fibrosis in the patient. In certain embodiments, the dose of NIR imaging agents is about 3 to about 5 nmol. In certain embodiments, an additional conjugate of the structure in included:

[0045] . ons can be made to the specific implementations described above. The implementations should not be limited to the particular limitations described. Other implementations may be possible. While the conjugates and pharmaceutical compositions are illustrated and described in detail in the foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only certain embodiments have been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected. Various techniques and mechanisms will sometimes describe a connection or link between two components. Words such as attached, linked, coupled, connected, and similar terms with their inflectional morphemes are used interchangeably, unless the difference is noted or made otherwise clear from the context. These words and expressions do not necessarily signify direct connections but include connections through mediate components. It should be noted that a connection between two components does not necessarily mean a direct, unimpeded connection, as a variety of other components may reside between the two components of note. Consequently, a connection does not necessarily mean a direct, unimpeded connection unless otherwise noted. Even still further provided is a ligand that targets fibroblast activation protein alpha (FAP^), wherein the ligand has the structure of formula (IX) or formula (X):RR6R5R4 R7R6R5R4O R78R3O R8R3 is a functionalized, 5- to 10-membered, N-containing, aromatic or non- heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic an alkyl primary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl amine; R1 is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6alkyl, -O-C1-6alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11 are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13is selected from the group of substituents consisting of -H, -D, Cl-Cl0alkyl, -C3-Cl0cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20 alkyl aryl is: from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which and R14a, R15a, R16a, and R17aare independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted; or R13 is are independently selected from the group of substituents consisting of -H, -D, -OMe, -C1-C3 alkyl, benzyl (Ph-CH2-), and substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted. The ligand that targets FAP^ can have the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:

[0046] R1is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6alkyl, -O-C1-6alkyl, -S-C1-6alkyl, -Cl-Cl0alkyl, -C3-Cl0cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26 are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted. R13 can be independently selected from the group of substituents consisting of O O O O O O EXAMPLES Materials & Equipment. All cell lines were originally purchased from ATCC (Manassas, VA). Cell culture media including RPMI-1640, and DMEM were purchased from GIBCO. 200-proof ethanol was purchased from Decon Labs, Inc. (King of Prussia, PA). All other cell culture reagents such as 2 mM glutamine, penicillin-streptomycin, and fetal bovine serum (FBS) were purchased from Life Technologies. Common cell culture materials such as syringes and culture flasks were acquired from VWR (Chicago, IL). Sterile BD insulin syringes were purchased from ADW® Diabetes (Pompano Beach, FL). Amine-coated 24-well cultureware plates were purchased from BD Biosciences (San Jose, CA). DOTA-NHS ester was purchased from Macrocyclics. acetic acid, DTPA, L methionine, TEA, DIPEA, DCM, DMF, DMSO, TFA, EtOH, MeOH, and ACN were purchased from Sigma-Aldrich (St. Louis, MO). Commercial reagents and solvents were all used without additional purification. Purifications were performed as indicated either by flash chromatography (Combi-Flash RF, Teledyne) or RP-HPLC (Agilent 1200 Instrument) with an XBridge OBD preparative column (19 x 150 mm, 5 μm) purchased from Waters (Milford, MA). NMR was performed with a Bruker 500 and 125 MHz NMR spectrometer equipped with a TXI cryoprobe. LC-MS was performed with an Agilent 1220 Infinity LC with a reverse-phase XBridge Shield RP18 column (3.0 x 50 mm, 3.5 μm). Radio-HPLC analysis was performed with an Agilent 1260 Infinity II equipped with a reverse-phase XBridge Shield RP18 column (.0 x 50 mm, 3.5 μm) and a Flow-RAM detector purchased from LabLogic (Brandon, FL). Radiolabeling was accomplished using a Fisherbrand Isotemp Digital Dry Bath / Block Heater (Waltham, MA). SPECT / CT scans were acquired with a VECTor / CT system with a clustered multi-pinhole high- energy collimator (MILabs, Utrecht, The Netherlands). All radioactive binding and biodistribution study samples were measured with a Hidex Automatic Gamma Counter (Hidex Oy, Turku, Finland). Experimental Procedures In vitro fluorescence and radioligand binding assays. HEK-hFAP cells (200,000 / well) were seeded into amine-coated, 24-well plates to ensure cell adherence. Following formation of monolayers, the cells were incubated at 4oC for 1 hour with the desired concentration of either FAP9-PEG3-FITC or111In-labelled FAP9-Ly-IP-Bn-DOTA or FAP9-PEG3-IP-Bn-DOTA conjugates in the presence or absence of excess unlabeled FAP9 ligand. Cells were then washed 3x with phosphate-buffered saline (PBS) to remove unbound fluorescence or radioactivity and then dissolved in 300 µl of 1% sodium dodecyl sulfate (SDS). The resulting solutions were then transferred into 96-well black plates (for quantitation of FAP9- PEG3-FITC fluorescence) or gamma counting tubes (for111In-labelled FAP9-Ly-IP-Bn-DOTA and FAP9-PEG3-IP-Bn-DOTA counting), and fluorescence was measured using a fluorescence NeO2 Plate Reader (ʎex= 488 nm and ʎem= 520 nm), while radioactivity was counted using a HidexAMG gamma counter. Cell-bound fluorescence or radioactivity was plotted against various concentrations of conjugate, and the apparent Kd values were determined using a one-site binding (hyperbola) curve-fitting program in GraphPad prism7. All experiments were performed in triplicate. Internalization study. Human FAP-transfected HT1080-FAP cells were (100,000) plated on 4 well confocal plates and incubated with various concentration ranging from (10nM, 25nM and 50 nM) FAP9- PEG3-FITC conjugate (15) for 1 h at 37oC. The unbound fluorescence was removed by washing the cells (3x500 µL) with medium, and cells were further incubated with growth media for different time points and cells-bound fluorescence was imaged using confocal microscopy. The experiments were done in triplicates Analysis of FAP ligand affinity and specificity. FAPα (catalog number: 3715-SE), PREP (catalog number: 4308-SE) and DPP4 (catalog number: 9168-SE-010) recombinant human enzymes were purchased from R&D Systems and enzyme buffer was obtained from BPS Bioscience. H-Gly-Pro-AMC and Z-Gly-Pro-AMC were purchased from Bachem Americas, Inc. Increasing concentrations of FAP9-Ly-IP-Bn-DOTA(34) conjugate was mixed with the appropriate fluorescent substrates for FAP, PREP (Z Gly-Pro-AMC) or DPP-IV (H-Gly-Pro-AMC) in enzyme buffer prior to addition of the desired enzyme (FAP, PREP or DPP-IV) and subsequent incubation at room temperature for 60 min. Fluorescence was then measured using a Cary Eclipse Fluorescence Spectrophotometer at an excitation wavelength of 380 nm and emission wavelength of 450 nm. All assays were performed in triplicate. Radiolabeling. FAP9-Ly-IP-Bn-DOTA or FAP9-PEG3-IP-DOTA or FAP10-Bn-DOTA or FAP10-IP-Bn- DOTA conjugates were dissolved in ammonium acetate buffer (NH4OAc) or Sodium acetate buffer (0.5M, pH 5.5) and labeled with [111In]InCl3 (BWMX Canada) or [177Lu]LuCl3 (National Isotope Development Center (NIDC), Oak Ridge National Laboratory) to obtain a specific activity of ≤ 3 MBq / nmol or ≤7.4 MBq / nmol, respectively. The resulting solutions were heated at 35oC for 10- 15 minutes and the radiopurities of the products were analyzed by radio-HPLC, (radio-HPLC method: a linear gradient from 5% B (acetonitrile) and 95% A (20 mM ammonium bicarbonate buffer) to 95% B over 15 minutes (see Fig.24). Radio purities exceeded >95% in all studies. Then DTPA (5 mM, pH 7.0) was added at a final concentration of 0.2 mM to chelate any unreacted traces of radionuclide. Followed by radiolabeled products were then formulated in 5% ethanol in PBS (v / v) containing 0.5% L-methionine (w / v) and 10% sodium ascorbate (w / v) and used without further purification for all studies. Animal models and husbandry. Mice were provided normal rodent chow and water ad libitum and maintained on a standard 12-hour light-dark cycle. All animal procedures were approved by the Purdue Animal Care and Use Committee. Tumor models. Balb / c mice were inoculated on their shoulders with 1 x 1054T1 cells, whereas nu / nu mice were inoculated on their shoulders with 5 x 106 cells HT29, MDA-MB-231, PANC-1or U87MG cells. Ex vivo radioligand biodistribution. Mice implanted with 4T1 tumors were intravenously injected with different doses (5 nmol / mouse) of FAP9-Ly-IP-Bn-DOTA or FAP9-PEG3-IP-Bn-DOTA or FAP10-IP-Bn-DOTA conjugate chelated with fixed amount of [177Lu] LuCl3(3.7 MBq / mouse). At the indicated times (4h, 24h, 48h, 96h, 168hand 288h post injection, n = 4 mice / time point), mice were euthanized by CO2 asphyxiation and organs of interest were harvested, rinsed, dried, weighed, and then measured by gamma counting. After correcting for decay, the results were plotted as the percentage of the injected dose per gram of tissue (%ID / g). Dosimetry analysis. From the biodistribution data above, the total absorbed radiation doses (mGy / MBq) were calculated using OLINDA 2.2.3 software. Dose estimates for healthy organs, such as blood, heart, lungs, liver, spleen, kidneys, and bone marrow, were calculated assuming a 25 g mouse phantom, whereas tumor dose estimates were calculated with the sphere model. Time-activity curves were fitted to the biodistribution data of each organ individually with exponential functions. SPECT / CT scans. SPECT / CT scans three different tumor-bearing mice (4T1, U87MG and RENCA n = 2) were injected intravenously with FAP9-Ly-IP-Bn-DOTA conjugate (5nmol / mouse) radiolabeled with ~14.8 MBq / mouse of [111In] InCl3. At the indicated times, mice were anesthetized and scanned using a MILabs VECTor / CT instrument. The SPECT scans were captured at a scan time of 20-60 minutes with a 0.35 mm pinhole (mouse whole body) collimator, with 15-60 second acquisitions per bed position across 50 bed positions. CT scans were captured with an X-ray source set at 615 μA and 60 kV. The SPECT images were reconstructed with U-SPECT II software using111In γ-energy windows of 171 and 241 keV. The CT images were reconstructed using NRecon software as described recently. A POS-EM algorithm was used with 16 subsets and 4 iterations on a 0.8 mm voxel grid. A 3.0 median filter was applied to all scans while background remover was only applied to remove low levels of noise seen outside the bodies of mice. To allow better tumor visualization the bladders uptakes were masked as needed for scans taken for the first time points at 4h and 24h post injection. No background remover was applied at any time points. Radionuclide therapy. 4T1 (n =5 / group), HT29 (n = 5 / group), MDA-MB-231(n= 5 / group), PANC-1(n = 5 / group) and U87MG tumor bearing mice were randomly divided into control and treatment groups to ensure similar average starting tumor volumes. Each cohort received a single intravenous injection of saline or [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA (37 MBq / mouse in case of 4T1, HT29, MDA-MB- 231, PANC-1 and U87MG tumor bearing mice, whereas 4T1 and U87MG tumor bearing mice were also treated with 18.5 MBq / mouse) chelated with 5nmol / mouse of conjugate (FAP9-Ly-IP- Bn-DOTA) on day 0, as indicated. Tumors were measured with a caliper in two perpendicular directions every other day, and mice were euthanized when body weight loss reached 20% or tumor volume exceeded 1500 mm3, according to Institutional Animal Care and Use Committee (IACUC) regulations. Statistical Analysis. Data was analyzed using GraphPad Prism 9 unless otherwise stated. All results are presented as mean ± SE. Statistical significance in tumor size was calculated using unpaired student’s t-test (*P < 0.05, **P < 0.01, ***P < 0.001 and ****P The following examples serve to illustrate the present disclosure. The examples are not intended to limit the scope of the claims in any way. Example 1 Synthesis of FAP9 ligand with free amine (14) (Fig.2) 1-(tert-butyl) 2-methyl (S)-4,4-difluoro-2-methylpyrrolidine-1,2-dicarboxylate (2): To a stirred solution of acid (500 mg, 1.908 mmol) in dry acetone (5 ml) were added K2CO3(1.5 eq) and methyl iodide (5 eq) and stirring at room temperature continued overnight. The reaction mixture was filtered, filtrate was evaporated under reduced pressure, and crude compound was purified by combi flash using ethyl acetate and hexane as mobile phase to obtain the desired compound (2) as a white solid. Synthesis of tert-butyl (S)-4,4-difluoro-2-formyl-2-methylpyrrolidine-1-carboxylate (3): To a stirred solution of 1-(tert-butyl) 2-methyl (S)-4,4-difluoro-2-methylpyrrolidine-1,2- dicarboxylate (1g, 3.77 mmol) in THF (10 mL) at 0oC was added LiBH4 (2.0 eq, 4M in THF) slowly dropwise. The reaction mixture was transferred to room temperature and stirring continued overnight. The reaction mixture further quenched by adding saturated sodium bicarbonate solution followed by extracted into CH2Cl2 (2x100mL) and the combined organic layer were dried over anhydrous sodium sulfate and evaporated under vacuum, and crude residue was purified by column chromatography using ethyl acetate hexanes as mobile offered to obtain the desired compound (3) (850 mg, 95% as white gummy liquid). Step ii Dess-Martin periodinane (4.92 g, 11.60 mmol) was added portion-wise to a solution of tert- butyl 4,4-difluoro-2-(hydroxymethyl) pyrrolidine-l-carboxylate (3) (2.5 g, 10.55 mmol) in CH2Cl2 (30 mL) and continued the stirring rt for 6h. Saturated NaHCO3 was added, and the layers were separated using a phase separator. The DCM was removed in vacuo to give a clear oil, which was purified by combi flash using ethyl acetate and hexanes as mobile phase to provide the desired aldehyde (4) (2.25g, 90%) as white solid. [Note: During the purification process of the aldehyde, it was noted that the compound remained undetected by ELSD. Consequently, all peaks were gathered, leading to the desired compound solidifying on the walls of the test tubes]. Synthesis of 4-(isocyanomethyl)-1,2-dimethoxybenzene (6): To a stirred solution of compound 5 (0.5g, 2.56mmol) in dry DCM (1.5 mL) at 0oC was added Et3N (5.0 eq, 12.82 mmol, 1.68 mL), followed by POCl3(1.5 eq, 3.84 mmol, 0.24 mL). The reaction was allowed to continue at the same temperature for 1 hour, and progress of the reaction was monitored by TLC. After completion of starting materials as indicated on TLC plates, the reaction mixture was diluted with DCM, absorbed on a silica-gel cartridge, and purified using ethyl acetate and hexanes as mobile phase to provide the desired compound (6) (750mg, 81%) as a light yellow liquid, which was slowly converted to light yellow solid upon storage. Synthesis of compound (9): A mixture of tert-butyl (S)-4,4-difluoro-2-formyl-2-methylpyrrolidine-1-carboxylate (4) (1 eq.200 mg, 0.851 mmol), N-protected glycine (7) (1 eq, 161mg, 0.851mmol) and isocyanide (6) (1 eq, 162 mg, 0.851 mmol) were dissolved in anhydrous CH2Cl2 and stirred for 4 hours. After complete conversion (LC-MS) of starting materials, trifluoroacetic acid (2.0 mL) was added, and the mixture was stirred for an additional 1 hour at room temperature. The volatiles were evaporated under reduced pressure. The oily residue was redissolved in anhydrous CH2Cl2 and cooled down to 0° C with an ice bath. Triethylamine (2.0 mL) was added dropwise and stirring continued until full conversion (LC-MS), which usually occurred in less than 2 hours. The liquids were evaporated under reduced pressure, and the mixture was redissolved in DCM and washed three times with water. Organic phase was washed with brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the crude residue was purified by using combiflash with hexanes + ethyl acetate as mobile phase to provide the desired α-hydroxyamide (8). The product was then used in the next step by dissolving in MeOH +AcOH (1:1) and adding 10%Pd-C (100 mg for 1g of starting material), then stirring under hydrogen atmosphere for 6 hours. The reaction mixture was filtered thorough celite pad, and the filtrate was evaporated under reduced pressure. The crude residue was azeotrope with EtOH and then purified by combiflash using MeOH +CH2Cl2to give the amine 9 as a brown-colored solid. Synthesis of compound (11): Route 1: To a solution of compound 10 (500 mg, 2.64mmol) in DMF (10. mL) were added Cs2CO3 (2.65 gm, 7.93 mmol) and then tertiary butyl bromo acetate (7.93 mmol). The reaction mixture was stirred at 55oC for 4 hours. Then KOH (7.93 mmol) and H2O (5.0 mL) were added to the same reaction mixture and stirring continued for an additional 2 hours. Progress of the reaction was monitored by LC-MS, the reaction mixture was carefully neutralized with 1N HCl, and the residue was purified by reverse phase combi flash using ammonium acetate buffer (20 mM; pH = 7.0) and acetonitrile as mobile phase to obtain the desired acid 10 as a white solid (650 mg; 81%). Route 2: To a solution of compound 10 (500 mg, 2.64 mmol) in DMF (5.0 mL), NaHCO₃ (2.0 eq) and benzyl chloride (1.2 eq) were added. The reaction mixture was stirred at 55°C overnight. Subsequently, Cs₂CO₃ (1.5 eq) and tert-butyl bromoacetate (2.0 eq) were added to the same reaction mixture, and stirring was continued at 55°C for an additional 2 hours. The reaction mixture was then diluted with water and extracted twice with ethyl acetate (2 × 50 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to yield a crude residue. The residue was purified using a CombiFlash system to afford the desired compound 10a in quantitative yield. Compound 10a was then used in the subsequent step. It was dissolved in methanol (MeOH), and 10% Pd-C (100 mg per 1 g of starting material) was added. The mixture was stirred under a hydrogen atmosphere for 4 hours, during which the product solidified in the reaction mixture. The solid was filtered using an Inner-Joint Improved Büchner Funnel (avoiding the use of a Celite pad). The precipitate was repeatedly dissolved in a 50% MeOH / CH2Cl2mixture to remove residual Pd- C, followed by filtration. The filtrate was concentrated under reduced pressure, and the crude residue was redissolved in ethyl acetate to precipitate the desired acid (11). The solid was dried under vacuum, yielding compound 11 as a white solid in quantitative yield. Synthesis of compound (12a): Step-1 To a stirred solution of compound 11 (200 mg, 0.66 mmol) in anhydrous CH2Cl2 (10.0 mL) was added PyBOP (411 mg, 0.792 mmol) and DIPEA (0.22 mL, 1.32 mmol), and stirring continued for 10 minutes. Amine 9 (0.66 mmol) was added to the above reaction mixture and stirring continued for an additional 2 hours. The reaction mixture was diluted with water and then extracted into CH2Cl2 (2x20 mL). The combined organic extracts were dried over anhydrous sodium sulphate and filtered. The filtrate was evaporated under reduced pressure to obtain a crude residue, which was purified by combiflash using MeOH+CH2Cl2 as mobile phase to provide the compound 12a as a white solid. Step-2 To a stirred solution of compound 12a (500 mg, 0.728 mmol) in CH2Cl2(10 mL) were added Dess– Martin periodinane (DMP) (3.0 eq, 2.186 mmol) and H2O (5.0 Eq). Stirring continued at room temperature for six hours, and the progress of the reaction was monitored by LCMS. The reaction mixture was further diluted with saturated sodium bicarbonate solution, followed by extraction into dichloromethane (CH2Cl2). The combined organic extracts were evaporated under reduced pressure, and the crude residue was purified by combiflash using methanol + dichloromethane to provide the desired keto compound (12b) as a white solid. Synthesis of compound (14): To a solution of compound 12b (200.0 mg, 0.297mmol) in CH2Cl2 (5 mL) was added TFA (2.0 mL). The mixture was stirred at room temperature for two hours. The reaction mixture was evaporated under reduced pressure and dried under vacuum. The crude residue was redissolved in CH2Cl2 (10.0 mL), followed by the addition of PyBOP (1.2 eq) + DIPEA (5.0eq). After 10 minutes of stirring, BocNH(PEG)3NH2(1.1 eq) was added, and stirring continued for an additional two hours. Work-up and purification followed the same procedure as described in the synthesis of compound 12a to provide compound 13 as a white solid. Then compound 13 was redissolved in CH2Cl2,treated with TFA, and evaporated under reduced pressure to give the targeted amine compound 14 as a gummy solid, which was utilized for further steps without purification. Example 2 Synthesis of FAP9-FITC conjugate (15) (Fig.3) General procedure for the synthesis of Compound 15: To a stirred solution of amine 14 in dry DMF was added 5-(((l1-sulfaneyl)-l3- methylene)amino)-3',6'-dihydroxy-3H-spiro[isobenzofuran-1,9'-xanthen]-3-one (1.0) followed by DIPEA (2.0 eq), and stirring continued at room temperature for 10 min. Then the reaction mixture was diluted with water and purified using uHPLC with A = 20 mM ammonium acetate (pH = 7), B = acetonitrile (5-35 method for 60 minutes). The FAP9-PEG3-FITC conjugate (compound 15) was obtained as a yellow solid. Example 3 General procedure for the synthesis of FAP9-PEG3-NOTA (17), FAP9-PEG3-DOTA (18) and FAP9-PEG3-Bn-DOTA (19) (Fig.4) To a stirred solution of amine 14 in three different reaction vials with dry DMF were added the respective chelators (1.2eq) (NHS-NOTA, NHS-DOTA and p-NCS-Bn-DOTA) and DIPEA (3. eq) and stirred at room temperature for 2-3 hours. Reaction mixtures were further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The respective conjugates (17-19) were obtained as white solids upon lyophilization. Example 4 Synthesis of FAP9 conjugates 22-24 (Fig.5) To a stirred solution of amine 14 (1.0 eq) in CH2Cl2were added acid (20) (1.0eq), PyBOP (1.2 eq with respect to acid), and DIPEA (3.0 eq), and stirring continued at room temperature for one hour. The reaction mixture was diluted with water, followed by extraction into CH2Cl2and purification as described using combiflash with methanol system to obtain the desired compound 21 as a white solid. Compound 21 was treated with diethyl amine, and the resultant amine was placed in three different reaction vials with dry DMF, to which were added the respective chelators (1.2eq) (NHS- NOTA, NHS-DOTA and p-NCS-Bn-DOTA) and DIPEA (3. eq). Stirring continued at room temperature for 2-3 hours. The reaction mixtures were further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The respective conjugates (22-24) were obtained as white solids upon lyophilization. Example 5 Synthesis of FAP9-LyCOOH-IP-Bn-DOTA (28) (Fig.6) The synthesis and purification of compound 28 followed the same procedure as described above in the synthesis of compounds 22-24 using appropriate starting materials. Example 6 General procedure for the synthesis of compounds 30a and 31 (Fig.7) To a solution of compound 12b (1.0 g 1.4619 mmol) in CH2Cl2(10 mL) was added TFA (10.0 mL) the stirred at rt for 2h, then reaction mixture was evaporated under reduced pressure and dried under vacuum, then resulted crude residue was purified by combiflash using methanol +dichloromethane as mobile provided compound 12c light yellow solid in 90% yield. The acid 12c (1.0 g, 1.589 mmol) was dissolved in CH2Cl2(10.0 mL), followed by PyBOP (1.2 eq) + DIPEA (3.0eq) were added. After 10 minutes stirring, to the above reaction mixture, 2-(((((9H-fluoren-9- yl)methoxy)carbonyl)-D-lysyl)oxy)-2-methylpropan-1-ylium (29) (1.1 eq) was added and continued stirring there for additional 2h, then reaction mixture was further diluted with water and extracted into dichloromethane (2x30 mL), the combined organic extracts were dried over anhydrous sodium sulphate, filtered and filtrate was evaporated under vacuum, the obtained crude residue was purified by using combiflash with methanol +CH2Cl2provided compound 30 as white solid, which was further dissolved in CH2Cl2and diethyl amine (1:1) and stirred at rt 2h, followed by evaporated under vacuum, then crude residue was purified by combiflash provided the free amine compound 30a as brown solid. Then to a stirred solution of compound 20 [5, 6](200 mg, 0.312mmol) in dichloromethane was added PyBOP (1.2 eq), DIPEA (3.0eq), followed by amine 30b was added and stirred for additional 2h. for work up and purification followed same procedure as described in the synthesis of compound 30a provided the compound 31a as white solid. Then compound 31a was redissolved in CH2Cl2, followed sequentially treated with diethyl amine followed by TFA, then evaporation under reduced pressure provided the amine 31b, which was used for further steps without purification Example 7 General procedure for the synthesis of compounds 32-36 (Fig.8). To a stirred solution of 31b (0.1g, 0.086 mmol) in different reaction vials in DMF (500 uL) were added DIPEA (3.0 eq) followed by respective chelators (NHS-NOTA or NHS-DOTA or p-SCN-Bn-DOTA or Macropa-NCS or 3p-C-NETA (1.5 eq) and stirred at for 3h. reaction mixtures were further diluted with water and purified by uHPLC (5-35% method consisting of A = ammonium acetate (10 mM, pH = 5.0 ) buffer, B = acetonitrile for 60 minutes provided the respective conjugates such as FAP9-Ly-IP-NOTTA (32), FAP9-Ly-IP-DOTA (33), FAP9-Ly-IP- Bn-DOTA (34), FAP9-Ly-IP-MACROPA (35) and FAP9-Ly-IP-3p-C-NETA (36) conjugates as white solids upon lypolization of uHPLC fractions. Example 8 Synthesis of FAP9-Pz-IP-NOTA (41), FAP9-Pz-IP-DOTA (42) and FAP9-Pz-IP-Bn-DOTA (43), FAP9-Pz-IP-MACROPA (44) and FAP9-Pz-IP-3p-C-NETA (45) conjugates (Fig.9) To a stirred solution of compound 38 (1.0 eq) in dry CH2Cl2 were added PyBOP (1.2eq) and DIPEA (3.0 eq). Stirring continued at room temperature for 10 min. Amine 9 (1.0 eq) was added to the reaction mixture and stirring continued for an additional two hours. The reaction mixture was diluted with water and extracted into CH2Cl2. Organic extracts were evaporated and purified by combiflash. The resulting hydroxy compound was further oxidized with Dess–Martin periodinane (DMP) in dichloromethane to provide compound 39 as a white solid. Further deprotection of the BOC group in compound 39 with TFA followed by reaction with the corresponding acid (20) provided the compound 40, which was further deprotected using diethyl amine in CH2Cl2 followed by reaction with respective (NHS-NOTA or NHS-DOTA or p-SCN- Bn-DOTA or Macropa-NCS or 3p-C-NETA to yield the compounds 41-45 as crude. The final compounds were further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The respective conjugates (41- 45) obtained as white solids upon lyophilization. Example 9 Synthesis of FAP10-Bn-DOTA and FAP10-IP-Bn-DOTA conjugates (Fig.10) Sequential coupling of compound 46 with compound 42 provided compound 47, which was further reacted with amine 9 to give compound 48. Oxidation of 48 with DMP followed by Fmoc deprotection of and subsequent reaction with naphthoyl chloride yielded the compound 51. Compound 51 was deprotected under acidic condition, followed by reaction with corresponding PEG acid to provide the compound 52. Then compound 2 was utilized for the synthesis of FAP10- Bn-DOTA (53) and FAP10-IP-Bn-DOTA (55) by reacting with respective starting materials. These final compounds were further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The respective conjugates (53 and 55) were obtained as white solids upon lyophilization. Example 10 Synthesis of FAP9-PEG1-NOTA (57), FAP9-PEG1-DOTA (58), FAP9-PEG1-Bn-DOTA (59) conjugates. Reaction of FAP9 base ligand (13a) with PEG1 amine provided the intermediate compound 56 as white solid. Which further treated with TFA and followed by reaction with NHS-NOTA, or NHS-DOTA or p-SCN-Bn-DOTA chelators provided the respective final conjugates (57-59). Example 11 Synthesis of different FAP9 conjugates having radiosentizers nitro imidazole moiety. The key intermediate (61) synthesized from appropriate starting material using literature methods. Then the intermediate 61 was coupled with different FAP9 linker amines provided the intermediate compounds 62-64 (Fig.11). Then, the Fmoc group in 62-64 were deprotected with (Et)2NH in dichloromethane provided the free amines, which were further reacted with NHS-ester of chelators provided final conjugates (Figs.12-14). All these conjugates were purified by using the same conditions as described above. Example 12 Synthesis of FAP9-PEG3 ICG Conjugate (Fig.16) To a stirred solution of amine 14 in DMF was added ICG-Osu (ICG NHS ester, Cat. No.: HY-D1041). Then stirring continued at room temperature for two hours under dark conditions. The reaction mixture was further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). Compound 74 was obtained as a green solid upon lyophilization. Example 13 Synthesis of FAP9-Ly-ICG Conjugate (Fig.16) To a stirred solution of amine 30 in DMF was added ICG-Osu (ICG NHS ester, Cat. No.: HY-D1041). Stirring continued at room temperature for two hours under dark conditions. Then the reaction mixture was further diluted with water and purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The FAP9-Ly-ICG conjugate (75) was obtained as a green solid upon lyophilization. Example 14 Synthesis of FAP9-PEG2-IP-S0456 conjugate (77) To a stirred solution of 3-(4-(tert-butoxy)phenyl)propanoic acid in dichloromethane was added PyBOP and DIPEA for 10 minute, then amine 27 was added to the reaction mixture and continued stirring for additional 2h. reaction mixture was further diluted with water and extracted into dichloromethane, then organic extracts were dried over anhydrous sodium sulphate, filtered, and filtrate was evaporated under reduced pressure and resulted crude residue was purified by combi flash provide the compound 76. Then the compound 76 was dissolved in dichloromethane, then treated with TFA, then resulted hydroxy compound was redissolved in DMSO, then added cl- S0456 and Cs2CO3 and stirred at rt 6h. Then the reaction mixture was diluted with water purified using uHPLC with A = 10 mM ammonium acetate (pH = 5), B = acetonitrile (5-35 method for 60 minutes). The FAP9-PEG2-IP-S0456 conjugate (77) was obtained as a green solid upon lyophilization. Example 15 Induced fit docking (IFD) The standard induced fit docking (IFD) protocol in the Schrodinger software package was used to dock the ligands of interest into the binding pocket of FAP. Firstly, a receptor grid box was generated by specifying the amino acid residues in FAP reported being involved in binding interactions. The IFD protocol utilizes the Glide docking protocol to generate up to 20 poses for each ligand which are further refined using the Prime Refinement module. The residues within 5Å of ligand poses were refined, and the side chains of the residues were optimized. Upon refinement of the binding site after initial docking, the ligands were re-docked into structures that are within 30.0 kcal / mol of the best structure and within the top 20 structures overall. The standard precision (SP) scoring function was used in the Glide redocking step to get the final docking scores. As seen in Figs.19-21 introduction of small alkyl groups, such as methyl, ethyl, propyl or butyl groups, and replacement of hydrogen with fluorine in FAP8 further increased binding interaction docking scores of the resultant analogues, referred to herein as FAP9 analogues. Example 16 In vitro fluorescence and radioligand binding assays HEK-hFAP cells (200,000) / well) were seeded into amine-coated 24-well plates to ensure cell adherence. Following formation of monolayers, the cells were incubated at 4oC for 1 hour with the desired concentration of either FAP9-FITC or111In- or177Lu-labelled FAP9-DOTA conjugates in the presence or absence of excess of unlabeled FAP9 ligand. Cells were then washed 3x with phosphate-buffered saline (PBS) to remove unbound fluorescence or radioactivity and then dissolved in 300 µl of 1% sodium dodecyl sulfate (SDS). The resulting solutions were then transferred into 96-well black plates (for quantitation of FAP9-FITC fluorescence) or gamma- counting tubes (for111In- or177Lu-labelled FAP9-DOTA counting), and fluorescence was measured using a fluorescence NeO2 Plate Reader (ʎex= 488 nm and ʎem= 520 nm), while radioactivity was counted using a HidexAMG gamma counter. Cell-bound fluorescence or radioactivity was plotted against various concentrations of conjugate, and the apparent Kd values were determined using a one-site binding (hyperbola) curve fitting program in GraphPad prism7 (Fig.22). All experiments were performed in triplicate. Head-to-head comparison of the binding affinities of FAP9-FITC (Compound 15) and FAP8-FITC on HEK-hFAP cells revealed that FAP9-FITC demonstrates superior affinity (Kd = 0.98 nM) compared to FAP8-FITC (Kd = 1.2 nM). Additionally, the observed suppression of FAP9-FITC binding upon incubation with a 100-fold excess of unlabeled FAP8 ligands confirms that the binding of FAP9-FITC to HEK-hFAP cells is mediated by FAP. Similarly, the binding studies depicted in Fig. 24A&B for [111In]In-FAP9-Ly-IP-Bn-DOTA (Compound 34) and [111In]In-FAP9-PEG3-IP-Bn-DOTA (Compound 24) (Fig.24C) on HEK+hFAP cells show that [111In]In-FAP9-Ly-IP-Bn-DOTA exhibits a binding affinity of Kd = 0.8 to 3.0 nM, whereas the binding affinity for [111In]In-FAP9-PEG3-IP-Bn-DOTA is Kd = ~2.0 nM. These values are 4-fold and 1.6-fold higher, respectively, than the binding constant for FAP8. Example 17 To determine the binding affinity and specificity of the FAP9-Ly-IP-Bn-DOTA conjugate (compound 34) (Fig. 8), the inhibition potency of compound against FAP was measured and its closest homologs, PREP and DPP-IV. As detailed in Fig.25, FAP8 preferentially inhibited FAP over PREP and DPP-IV, with half-maximal inhibitory concentrations of 0.26-0.38nM, and more than 3,000 nM, respectively, Introduction of the additional methyl group onto the FAP9 ligand significantly improved its selectivity for FAP over PREP by ~3500-fold relative to FAP8 [6]. Example 18 SPECT / CT scans Tumor-bearing mice (mouse breast cancer 4T1), U87MG (human glioblastoma) and RENCA (mouse kidney) were injected intravenously with FAP9-Ly-IP-Bn-DOTA (Compound 34; Fig.18) conjugate radiolabeled with ~13 to 18.5 MBq of indium-111. At various times, mice were anesthetized and scanned using a MILabs VECTor / CT instrument. CT scans were reconstructed using NRecon software. The datasets were fused, filtered, and processed using PMOD software (version 3.2) as recently reported. As shown in Figs. 29-33, the whole-body SPECT-CT images collected at various timepoints revealed that [111In] In-FAP9-Ly-IP-Bn-DOTA accumulated rapidly in 4T1, U87MG and RENCA tumors, where it remained for at least 168 to- 288hours. In contrast, most of the radioactivity in the healthy tissues was cleared by 24 hours post- injection. Further head -to head imaging comparison of [111In]In-FAP9-Ly-IP-Bn-DOTA with [111In]In-FAP2286 in RENCA tumor bearing mice revealed that, [111In]In-FAP9-Ly-IP-Bn-DOTA exhibits >50x better tumor retention than [111In]In-FAP2286 (>192h vs <4h) (see Fig. 33 and Fig.34). Similar results were also observed with [111In] In-FAP9-PEG3-IP-Bn-DOTA in the same 4T1 tumor bearing mice (Fig.43). Example 19 Biodistribution analysis Mice implanted with 4T1 tumors were intravenously injected with [111In] In-FAP9-Ly-IP- Bn-DOTA (Compound 34; Fig.18) (0.74MBq / mouse, 5.0 nmol / mouse) or [111In] In-FAP9-PEG3- IP-Bn-DOTA (Compound 24; Fig.21). At the indicated times (4h, 24h, and 144h, post-injection), mice were euthanized by CO2 asphyxiation and organs of interest were harvested, rinsed, dried, weighed, and then analyzed by gamma counting. After correcting for decay, the results were plotted as the percentage of the injected dose per gram of tissue (%ID / g) (Figs.29 and 43). Analysis of the resulting biodistribution data revealed that mice injected with [111In]-In- FAP9-Ly-IP-Bn-DOTA exhibited 7.5 % ID / g tumor uptake, which increased to ~14% ID / g by 24 hours and then gradually declined to 8.7% ID / g by 144 hours post-injection. The radioactivity of other healthy tissues, such as blood, liver, spleen and kidney, significantly reduced by 24 hours post-injection. Similar results were also observed with [111In]In-FAP9-PEG3-IP-Bn-DOTA, but tumor uptake (3.8 % ID / g) with this conjugate at 144 hours was 2.2-fold lower than the tumor uptake of [111In]In-FAP9-Ly-IP-Bn-DOTA (3.8 % ID / g vs 8.7% ID / g) (Fig. 29 and Fig.43). Similarly, in another experiments, 4T1 tumor bearing mice were injected with [177Lu]Lu-FAP9- Ly-IP-Bn-DOTA (3.7 MBq / mouse, 5nmol / mouse) and biodistribution analysis at different time points (4h, 24h, 48h, 96h, 168h and 288h) indicates the [177Lu]Lu-FAP9-Ly-IP-Bn-DOTA exhibits ~10 %ID / g at early time points (4h, 24h and 48h post-injection), the tumor uptake further gradually reduced to 1.5% ID / g by 288h post-injection. Whereas the radioactivity uptake in the healthy tissues was minimal and significantly cleared by 48h post-injection (Fig.35A). Mice implanted with 4T1 tumors were intravenously injected with [177Lu] Lu-FAP10-IP- Bn-DOTA or [177Lu] Lu-FAP10-DOTA (7.4 MBq / mouse, 5 nmol / mouse). At various times (4 hours, 24 hours, and 120 hours post-injection), mice were euthanized by CO2asphyxiation and organs of interest were harvested, rinsed, dried, weighed, and then analyzed by gamma counting. After correcting for decay, the results were plotted as the percentage of the injected dose per gram of tissue (%ID / g). Analysis of the resulting biodistribution data revealed that mice injected with [177Lu]-Lu-FAP10-IP-Bn-DOTA exhibited ~6.5 % ID / g tumor uptake at 4 hours and 24 hours post-injection, which gradually declined to 2%ID / g by 120 hours post-injection, whereas [177Lu]- Lu-FAP10-Bn-DOTA exhibited 3.5 %ID / g and ~2 %ID / g at 4 hours and 24 hours post-injection, respectively, which dropped down to ~0.2 %ID / g. The biodistribution results are shown in the top panels of Fig.44, whereas the calculated tumor: healthy tissues ratios are shown in the bottom panels of Fig.44. Table-1: Biodistribution analysis of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA in 4T1 tumor bearing mice. Tissues 4h 24h 48h 96h 168h 288h %ID / g (n=5) (n=5) (n=5) (n=5) (n=5) (n=5) Example 20 Dosimetry analysis From the biodistribution data above, the total absorbed radiation doses (mGy / MBq) were calculated using OLINDA 2.2.3 software. Dose estimates for healthy organs, such as blood, heart, lungs, liver, spleen, kidneys, and bone marrow, were calculated assuming a 25 g mouse phantom, whereas tumor dose estimates were calculated with the sphere model. Time-activity curves were fitted to the biodistribution data of each organ individually with exponential functions. As shown in Fig. 29 (lower panel), with [111In] In-FAP9-Ly-IP-Bn-DOTA conjugate (Compound 34), the total absorbed radiation dose in tumor was 245 mGy / MBq which is 11x, 15x, 5.1x, 6.5x, 5x and 14.5x higher than the total observed radiation dose in heart, lungs, liver, spleen, kidneys, and bone, respectively. Similarly, as shown in Fig. 43, with [111In] In-FAP9-PEG3-IP- Bn-DOTA conjugate (Compound 24), the total absorbed radiation dose in tumor was 131 mGy / MBq, which is 12x, 16.11x, 3.2x, 5.0 x, 2.6x and 6.55x higher than the total absorbed radiation dose in heart, lungs, liver, spleen, kidneys, and bone, respectively. Similarly, from biodistribution data of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA in 4T1 tumor bearing mice, the total absorbed radiation dose in tumor was 1004 mGy / MBq which is 8x, 13x, 6.0x, 9x, 8.5x and 12x higher than the total observed radiation dose in heart, lungs, liver, spleen, kidneys, and bone, respectively (Fig.35B). On the basis of external-beam radiation (not RPT) studies, the Food and Drug Administration has recommended that total cumulative radiation doses to healthy tissues limited to less than 20 Gy for heart, less than 7 Gy for lungs, less than 30 Gy for liver, and less than 23 Gy for kidneys (Fig.36A). Because radiosensitive tumors respond at about 40 Gy whereas radioresistant tumors may require upto100 Gy to shrink (Fig.36A), the tumor–to– healthy-organ dosimetry ratios necessary for safe therapeutic index can be determined. Assuming that tumor radiation doses should exceed about 100 Gy, with maximum kidney, and liver, cumulative exposures remaining below 23, and 30, respectively, a conservative estimate suggests that tumor-to-kidney, and tumor-to-liver need to exceed 4.34, and 3.3 respectively. Compliance with these minimum ratios would ensure effective tumor shrinkage without significant normal- tissue toxicity. As shown in Fig.36b [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA achieved the all required tumor-to-healthy tissues ratios even treatment of highly radio resistance tumors. Example 21 Radionuclide therapy and toxicology 4T1 (n =5 / group), HT29 (n = 5 / group), MDA-MB-231(n= 5 / group), PANC-1(n = 5 / group) and U87MG tumor bearing mice were randomly divided into control and treatment groups to ensure similar average starting tumor volumes. Each cohort received a single intravenous injection of saline or [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA (37 MBq / mouse in case of 4T1, HT29, MDA-MB- 231, PANC-1 and U87MG tumor bearing mice, whereas 4T1 and U87MG tumor bearing mice were also treated with 18.5 MBq / mouse) chelated with 5nmol / mouse of conjugate (FAP9-Ly-IP- Bn-DOTA) on day 0, as indicated. Tumors were measured with a caliper in two perpendicular directions every other day, and mice were euthanized when body weight loss reached 20% or tumor volume exceeded 1500 mm3, according to Institutional Animal Care and Use Committee (IACUC) regulations. As shown in Figs. 37–41, treatment with 37 MBq of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA resulted in tumor growth rate reductions of 94%, 90%, 95%, 90%, and 75% in the MDA-MB-231, 4T1, PANC-1, HT29, and U87MB tumor xenograft models, respectively, compared to the untreated group. Similarly, in selected tumor models (4T1, HT29, and U87MG), administration of a lower specific activity dose of 18.5 MBq of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA led to significant tumor growth reductions of 86%, 83%, and 84%, respectively, compared to control mice. To determine whether any overt toxicities were caused by [177Lu] Lu-FAP9-Ly-IP-Bn- DOTA treatment, tissue sections from the heart, lung, liver, spleen and kidneys of all treated and untreated control groups were examined by a board-certified veterinary pathologist after hematoxylin and eosin staining in HT29 tumor models. No diagnostic lesions or other morphologic abnormalities were detected in the HT29 tumor–bearing mice (Fig.42) further confirm the safety and efficacy of [177Lu] Lu-FAP9-Ly-IP-Bn-DOTA treatments. Example 22 Synthesis of FAP9-S0456 conjugate (16) (Fig.48) Synthesis of 1-(tert-butyl) 2-methyl (S)-4,4-difluoro-2-methylpyrrolidine-1,2- dicarboxylate (2): To a stirred solution of acid (500 mg, 1.908 mmol) in dry acetone (5 ml) were added K2CO3 (1.5 eq) and methyl iodide (5 eq). Stirring at room temperature was continued overnight, the reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The crude compound was purified by combi flash using ethyl acetate and hexane as mobile phase. The desired compound 2 was obtained as a white solid. Synthesis of tert-butyl (S)-4,4-difluoro-2-formyl-2-methylpyrrolidine-1-carboxylate (3): To a stirred solution of 1-(tert-butyl) 2-methyl (S)-4,4-difluoro-2-methylpyrrolidine-1,2- dicarboxylate (1g, 3.77 mmol) in THF (10 mL) at 0oC was added LiBH4 (1.1 eq, 4M in THF) slowly dropwise. The reaction mixture was transfered to room temperature and stirring continued for one hour. The reaction mixture was evaporated under vacuum, and the residue was redissolved in CH2Cl2 (100 mL), followed by extraction with saturated aqueous sodium bicarbonate solution (50 mL). The organic layer was separated and evaporated under vacuum. The crude residue was purified by column chromatography using ethyl acetate hexanes as mobile phase. The desired compound (3) was obtained as a white gummy liquid (850 mg, 95%). Step-ii: Dess-Martin periodinane (4.92 g, 11.60 mmol) was added portion-wise to a solution of tert- butyl 4,4-difluoro-2-(hydroxymethyl) pyrrolidine-l-carboxylate (3) (2.5 g, 10.55 mmol) in DCM (30 mL) at 0 °C. After complete addition, the reaction was warmed to room temperature and stirred for 2 hours. Saturated NaHCO3was added, and the layers were separated using a phase separator. The DCM was removed in vacuo to give a clear oil, which was purified by combi flash using ethyl acetate and hexanes as mobile phase to provide the desired aldehyde 3 (2.25g, 90%) as a white gummy liquid. (Note: during purification of aldehyde, it has been observed that compound was not detected by ELSD, so all peaks were collected. After purification the formation of white solid on test tubes could be seen in 15-20 minutes). Synthesis of 4-(isocyanomethyl)-1,2-dimethoxybenzene (5): To a stirred solution of compound 4 (0.5g, 2.56mmol) in dry DCM (1.5 mL) at 0oC was added Et3N (5.0 eq, 12.82 mmol, 1.68 mL), followed by POCl3 (1.5 eq, 3.84 mmol, 0.24 mL). The reaction was continued at the same temperature for one hour, and progress of the reaction was monitored by TLC. After completion of starting materials as indicated on TLC plates, the reaction mixture was further diluted with DCM, absorbed on silica-gel cartridge, and purified using ethylacetate+hexanes as mobile phase. The desired compound 5 (750mg, 81%) was obtained as a light yellow liquid; it was slowly converted to light yellow solid upon storage. Synthesis of compound (9): A mixture of N-Boc-L-prolinal (1 eq. 200 mg, 0.851 mmol), N-protected glycine (1 eq, 161mg, 0.851mmol) and isocyanide (1 eq, 162 mg, 0.851 mmol.) were dissolved in anhydrous DCM and stirred for four hours. After complete conversion (LC-MS) of starting materials, trifluoroacetic acid (2.0 mL) was added, and the mixture was stirred for one hour. The volatiles were evaporated under reduced pressure. The oily residue was redissolved in anhydrous DCM and cooled down to 0° C with an ice bath. Triethylamine (2.0 mL) was added dropwise, and the stirring continued until full conversion (LC-MS), usually less than 2 hours. The liquids were evaporated under reduced pressure, and the mixture was redissolved in DCM and washed three times with water. The organic phase was washed with brine and dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The crude residue was purified by using combiflash with hexanes + ethyl acetate as mobile phase to provide the desired α-hydroxyamide. The product was then used in the next step by dissolving in MeOH +AcOH (1:1) and adding 10%Pd-C (100 mg for 1g of starting material), followed by stirring under hydrogen atmosphere for 6 hours. The reaction mixture was filtered thorough celite pad, and the filtrate was evaporated under reduced pressure. The crude residue was azeotrope with EtOH, then purified by combiflash using MeOH +DCM to give the amine 9 as an orange colored solid. Synthesis of compound (11): To a solution of compound 10 (500 mg, 2.64mmol) in DMF (10. mL) was added Cs2CO3 (2.65 gm, 7.93 mmol), followed by tertiary-butyl bromo acetate (7.93 mmol). The reaction mixture was stirred at 55oC for four hours. Then KOH (7.93 mmol) and H2O (5.0 mL) were added to the same reaction mixture, and stirring was continued for an additional two hours. Progress of the reaction was monitored by LC-MS. The reaction mixture was carefully neutralized with 1N HCl, the residue was purified by reverse phase combi flash using (20 mM, pH= 7.0 ammonium acetate buffer) and acetonitrile as mobile phase to give the desired acid 11 as a white solid (650 mg 81%). Synthesis of compound (12): To a stirred solution of compound 11 (200 mg, 0.66 mmol) in anhydrous CH2Cl2(10.0 mL) were added PyBOP (411 mg, 0.792 mmol) and DIPEA (0.22 mL, 1.32 mmol), and stirring continued for 10 minutes. Amine 9 (0.66 mmol) was added to the above reaction mixture and stirring continued for an additional two hours. The reaction mixture was diluted with water and extracted into DCM (2x20 mL), and the combined organic extracts were dried over anhydrous sodium sulphate and filtered. The filtrate was evaporated under reduced pressure, and the crude residue was obtained and purified by combiflash using MeOH+DCM as mobile phase to obtain the compound 12 as a white solid. Synthesis of compound (13): To a stirred solution of compound 12 (1.0 eq) dissolved in DCM followed by DMP (3.0 eq) water (5.0. eq) was added. The solution was stirred at room temperature overnight. The reaction mixture was further diluted with saturated sodium bicarbonate solution and extracted into DCM (2x30 mL). The combined organic extracts were dried over anhydrous sodium sulphate and filtered. The filtrate was evaporated under reduced pressure, and the crude residue was purified by combiflash using MeOH +DCM as mobile phase to obtain the desired keto compound 13 as a white solid. Synthesis of compound (14): To a solution of compound 13 (200.0 mg, 0.297mmol) in DCM (5 mL) was added TFA (2.0 mL). The mixture was stirred at room temperature for two hours. The reaction mixture was evaporated under reduced pressure and dried under vacuum. The crude residue was redissolved in DCM (10.0 mL), followed by the addition of PyBOP (1.2 eq) + DIPEA (5.0eq). After 10 minutes of stirring, tert-butyl 3-(2-(2-aminoethoxy)ethoxy)propanoate (1.1 eq) was added, and stirring continued for an additional two hours. Work up and purification followed the same procedure as described above in the synthesis of compound 12 to provide compound 14 as a white solid. Synthesis of compound (15): To a stirred solution of compound 13 (200 mg, 0.237mmol) in DCM (5.0 mL) was added TFA (1 ml) at room temperature and continued stirring for 2 hours. The reaction mixture was evaporated under reduced pressure, and the crude residue was reduced with diethyl ether and filtered. The solid was dried and used in further steps without purification. Briefly, acid from compound 14 was redissolved in DCM followed by PyBOP (1.2 eq), then DIPEA (5 eq) was added and stirring continued for an additional 5 min, followed by the addition of (S)-1-(tert-butoxy)-3- (4-(tert-butoxy)phenyl)-1-oxopropan-2-aminium salt. Stirring continued at room temperature for two hours. The reaction mixture was diluted with water and extracted into DCM (2x15 mL). Organic extracts were combined and evaporated under reduced pressure. The crude compound was purified by combiflash with DCM and methanol as mobile phase to provide the compound 15a. Compound 15a was further redissolved in DCM followed by treatment with TFA to deprotect the tertiary butyl groups and rota-vaped under vacuum. The crude residue was purified using normal phase combi flash with methanol +dichloromethane system to provide compound 15b as a white solid. Synthesis of FAP9-PEG2-S0456 conjugate (compound-16): To a stirred solution of compound 15b (15 mg, 0.0157 mmol) in dry DMSO (500 μL) was added Cs2CO3 (10 eq, 0.157 mmol) followed by Cl-S0456 (1.3eq, 0.0204 mmol). Stirring continued at room temperature for five hours. The reaction mixture was diluted with water and purified by using uHPLC (A = 20 Mm ammonium acetate buffer (pH = 7), B =0 acetonitrile, solvent gradients 5% B to 35% in 60 min) to provide the desired compound 16 as a fluffy green solid (6.0 mg, 66%). Example 23 Synthesis of FAP9-S0456 with different PEG lengths (Fig.49) The synthesis and purification of compounds 20a-d followed the same experimental procedures as described for the synthesis of compound 16. Example 24 Binding analysis of FAP9-S0456 conjugate HEK-FAP cells (200,000 cells / well) were seeded in a 24-well plate. The cells were allowed to grow as a monolayer over 24 hours and were incubated with various concentrations of FAP9- S0456 conjugate either in the presence or absence of excess of competition ligand (ligand without dye). After incubating for 1 hour at 4ºC, the cells were washed three times with phosphate-buffered saline (PBS) to remove unbound fluorescence. The cells were then dissolved in 1% SDS, and the cell-bound fluorescence was measured using a fluorescence spectrophotometer by excitation / emission as.776 / 810 nm. As shown in FIG.50, FAP9-S0456 conjugated exhibited a binding constant Kd = 1.9 nM. Incorporation of the bulky S0456 dye onto the FAP9 ligand did not affect its FAP binding properties. Example 25 In vivo fluorescence imaging and biodistribution Female athymic nu / nu mice (5-6 weeks old) were purchased from Harlan Laboratories and allowed access to normal rodent chow and water ad libitum. The animals were maintained on a standard 12-hour light-dark cycle. All animal procedures were approved by the Purdue Animal Care and Use Committee. Female nu / nu athymic mice (5–6 weeks old) were subcutaneously injected with 5 × 10⁶ KB, MDA-MB-231, HT-29, U87MG, MIA PaCa-2, or A549 cells in 0.1 mL of sterile PBS. Whereas syngeneic tumors, including 4T1 (mouse breast cancer), CT26 (mouse colon cancer), and RENCA (mouse kidney cancer), were established by injecting 1 × 10⁵ of the respective cells in 0.1 mL of PBS. Tumors were allowed to grow to approximately 400-500 mm3before initiating imaging studies. Each tumor-bearing mouse was intravenously injected (via tail vein) with the 5.0 nmol of fluorescent dye conjugate (FAP9-S0456 conjugate) either in the presence or absence of a 200-fold excess of unlabeled ligand (FAP9 base ligand). Whole body images were acquired using Spectral Ami Optical Imaging System at different time points four hours post-injection followed by euthanasia using CO2asphyxiation. After performing whole-body imaging, organs of interest were harvested and imaged to quantitate fluorescence accumulation. The image acquisition parameters were as follows: (i) lamp level-high, (ii) excitation-745 nm, (iii) emission-810, (iv) binning (M) 4M, (v) f-stop-4, (vi) FOV-12.5, (vii) acquisition time, 5 sec, and (viii) power 55. To determine whether FAP9-S0456 might be capable of imaging a more physiologically relevant tumor model, FAP-negative HT29 cell tumors, whose sole FAP content is derived from naturally infiltrating FAP+ CAFs, were implanted into mice, and the ability of FAP9-S046 to image the tumors was examined. After allowing the tumor masses to grow to ~400 mm3, the mice were injected intravenously with FAP9-S0456 conjugate (5 nmol / mouse) and imaged 4 hours later. As shown in FIG. 51, strong fluorescence was visible at the tumor. Besides the tumor, the kidneys (i.e., where the conjugate undergoes excretion) were the only healthy tissues that became fluorescent. It was concluded that good tumor to background ratios could be achieved. In addition, tumor fluorescence in mice co-injected with a 200-fold excess of unlabeled FAP9 base ligands confirmed that fluorescence uptake in the targeted mice was mediated by FAP. Next, because CAFs are reported to accumulate in virtually all solid tumors, the question arose whether other tumor types might similarly recruit sufficient CAFs to enable FAP9-S0456 imaging. To address this question, different cancer cell lines deriving from distinct tumor types, namely, human colorectal cancer (HT29) (FIG. 52), human nasopharyngeal cancer (KB) (FIG. 54), murine breast cancer (4T1) (FIG.53), and human triple-negative breast cancer (MDA-MB- 231) (FIG. 54) were selected, and cells were implanted in appropriate recipient mice. After allowing tumors to grow to ~400 mm3, mice were similarly injected with 5 nmol FAP9-S0456 and again imaged 4 hours later. As shown in FIGs. 52-54, FAP9-S0456 conjugate displayed good uptake in all tumor types, with excellent tumor to background ratios. These data further confirm the utility of a FAP9-S0456 conjugate as an imaging agent for multiple tumor types. Further, the tumor uptake was FAP-mediated as clearly established by comparing the tumor accumulation of FAP9-S0456 conjugate in mice simultaneously injected with either saline or a competing concentration (200x) of unlabeled FAP9 base ligand (15a). Thus, as seen in all competition groups of whole body and biodistribution images, tumor retention was blocked by FAP9 base ligand (15a), while excretion through the kidneys was not. In fact, the only healthy tissue that showed significant fluorescence at this 4-hour time point was the kidney, where FAP9-S0456 was still undergoing excretion. To compare the tumor uptake and tumor:healthy tissues ratios of FAP9-S0456 with FAP8- S0456 conjugate, different mice bearing HT29 tumors were intravenously injected with one or the other conjugate (5 nmol / mouse). Whole-body and ex vivo biodistribution images were acquired at 4-hours post-injection. As shown in FIG. 55, FAP8-S0456 exhibited significantly high liver uptake at this time. In contrast, FAP9-S0456 showed very clean biodistribution. Further quantification of fluorescence in healthy tissues revealed that FAP9-S0456 conjugate exhibited significantly high fluorescence intensity, which was 25x, 22x, 13x, >50x and 0.86x higher than fluorescence intensity in heart, lungs, liver, spleen, and kidneys, respectively. In contrast, the tumor fluorescence intensity exhibited by FAP8-S0456 conjugate was only 7x, 1.94x, 0.67x, 47x, and 1.1x higher than fluorescence intensity in heart, lungs, liver, spleen, and kidneys, respectively (FIG. 56). To determine the optimal dose of FAP9-S0456 for improved tumor-to-healthy tissue contrast, enhancing visualization and resection of cancer nodules, FAP9-S0456 conjugate was intravenously administered at doses of 3 nmol, 5 nmol, and 10 nmol per mouse to six different tumor-bearing models: 4T1, RENCA, CT26, MDA-MB-231, A549, and MIA PaCa-2 (FIGS.57– 66). Whole-body imaging and ex vivo biodistribution analysis were performed at 4 hours post- injection. Fluorescence quantification revealed a consistent distribution pattern across all doses, with predominant accumulation in tumors and kidneys, though with varying intensity. Mice injected with the 10 nmol dose showed slightly increased liver uptake compared to those receiving 3 or 5 nmol. Among the three doses, the 5 nmol group exhibited optimal tumor intensity and the highest tumor-to-healthy tissue ratio. Example 26 Conjugate FAP9-S0456 was used to treat RENCA cell tumors in Balb / c mice. Doses of 3 nmol, 5 nmol and 10 nmol / mouse were utilized. Whole body and ex vivo images acquired at 4 hours post-injection. Excitation / emission were 745 / 810 nm. All three doses exhibited a similar distribution pattern, predominantly in the tumor and kidneys, but with varying fluorescent intensities. See Fig. 67. The 10 nmol dose showed minimal liver uptake compared to the other doses. The conclusion is that any dose between 3-5 nmol would be optimal. Example 27 Conjugate OTL38 was used to treat RENCA cell tumors in Balb / c mice (folate-free diet). Doses of 3 nmol, 5 nmol and 10 nmol / mouse were utilized. Whole body and ex vivo images acquired at 4 hours post-injection. Excitation / emission were 745 / 810 nm. All three doses exhibited a similar distribution pattern, predominantly in the tumor and kidneys, but with varying fluorescent intensities. The 10 nmol dose exhibited nonspecific uptake in the healthy tissues compared to the other doses. See Fig.68. The 5 and 10 nmol dose is also showing a warning of overexposed pixels in the image. The conclusion is that any does between 3-5 nmol would be optimal. All three doses of OTL38 exhibit 1.5-5x higher tumor fluorescence intensity compared to mice injected with FAP9-S0456, likely due to a greater number of FRβ+ cells than FAP+ cells. See Fig. 69. However, FAP9-S0456 shows better tumor-to-healthy tissue ratios than OTL38. An optimal dose for FAP9-S0456 could be between 5 nmol, while for OTL38, a dose between 3-5 nmol could be optimal. Example 28 A conjugate comprising FAP9-S0456 and OTL38 was used to treat RENCA Mouse kidney cancer tumors. Doses of 5 nmol of FAP9-S0456 + 2 nmol of OTL38 were utilized. Whole body and ex vivo images acquired at 4 hours post-injection. Excitation / emission were 745 / 810 nm. See FIG.70. In the cocktail imaging, the net tumor fluorescent intensity increased by 2.2-fold compared to targeting folate alone (9.25 e8 vs.4.14 e8) and approximately 3-fold compared to targeting FAP alone (9.25 e8 vs 2.95e8). See Fig.71. The tumor-to-healthy tissue ratios were further enhanced in the cocktail images compared to OTL38 alone (1.5 to 2.3x). Tumor: muscle ratios of cocktail vs OTL38 (6.1 vs 4.3). Example 29 Dose Escalation Study with OTL-38 in 4T1 Tumor Bearing Mice Mice were dosed with 3.0, 5.0, or 10.0 nmol / mouse and given whole body imaging (FIG. 72). Tumor, heart, lungs, liver, spleen, stomach, intestine, muscle and kidneys were observed. All three doses exhibited a similar distribution pattern, predominantly in the tumor and kidneys, but with varying fluorescent intensities. The 10 nmol dose showed slightly higher liver and stomach uptake compared to the other doses. The 10 nmol dose is also shows a warning of overexposed pixels in the image. Example 30 4T1 Tumors: Quantification of Fluorescent Intensity Plots of fluorescent intensity for tumor, heart, lungs, liver, spleen, stomach, intestine, muscle and kidneys for OTL38 and FAP9-S0456 using 3.0, 5.0, or 10.0 nmol / mouse doses are shown in FIG.73. All three doses of OTL38 exhibit 3-5 times higher tumor fluorescence intensity compared to mice injected with FAP9-S0456, likely due to a greater number of FRβ+ cells than FAP+ cells. However, FAP9-S0456 shows better tumor-to-healthy tissue ratios than OTL38. An optimal dose for FAP9-S0456 might be between 5-10 nmol, while for OTL38, a dose between 3- 5 nmol could be optimal. Example 31 OTL38: Dose Escalation in RENCA Tumor Bearing Mice Mice were dosed with 3.0, 5.0, or 10.0 nmol / mouse and given whole body imaging (FIG. 74). Tumor, heart, lungs, liver, spleen, stomach, intestine, muscle and kidneys were observed. All three doses exhibited a similar distribution pattern, predominantly in the tumor and kidneys, but with varying fluorescent intensities. The 10 nmol dose exhibited nonspecific uptake in the healthy tissues compared to the other doses. The 5 and 10 nmol dose is also showing a warning of overexposed pixels in the image. The results show that any dose between 3-5 nmol dose could be an optimal. Example 32 Quantification Fluorescent Intensity and T:Healthy Tissues Ratios in RENCA Tumors In RENCA tumor studies, all three doses of OTL38 exhibit 1.5-5x higher tumor fluorescence intensity compared to mice injected with FAP9-S0456, likely due to a greater number of FRβ+ cells than FAP+ cells (FIG. 75). However, FAP9-S0456 shows better tumor-to-healthy tissue ratios than OTL38. An optimal dose for FAP9-S0456 could be between 5 nmol, while for OTL38, a dose between 3-5 nmol could be optimal. Example 33 CT26 Tumor: Imaging with Optimal Dose of OTL38 at 4 hours Post-Injection 2 nmol doses of OTL38 were administered to Blab / c mice in a CT26 tumor study. Conjugates: OTL-38.4 hours post dose, excitation / emission of 745 / 810 nm were utilized. Results are shown in FIG.76. Example 34 OTL38: Dose Escalation in MDA-MB-231 Tumor Bearing Mice Doses of Conjugate OTL38 were administered to mice with tumor type MDA-MB-231 cells in nude mice (folate-free diet). Doses of 2 nmol, 5 nmol and 10 nmol / mouse were utilized. Whole body and ex vivo images acquired at 4 hours post-injection using an excitation / emission: 745 / 810 nm. All three doses exhibited a similar distribution pattern, predominantly in the tumor and kidneys, but with varying fluorescent intensities (FIG. 77). The 10 nmol dose exhibited nonspecific uptake in the healthy tissues compared to the other doses. The 5 and 10 nmol dose is also showing a warning of overexposed pixels in the image. As such, it is believed that any dose between 2-5 nmol dose could be an optimal dose. Example 35 OTL38: Dose Escalation in A549 Tumor Bearing Mice Conjugate OTL38 was delivered to tumor type: A549 cells in nude mice. Doses: 2 nmol, 5 nmol and 10 nmol / mouse were utilized. Results are shown in FIG.78. Both 5 and 10 nmol doses exhibits nonspecific uptakes in healthy tissues. An optimal dose could be 3 nmol. Example 36 MIA PaCa-2 Tumor Imaging 4 hours Post-Injection Doses of 5 nmol of FAP9-S0456 and 2 nmol of OTL38 were administered to mice with MIA PaCa-2 tumors. Images are shown in FIG.79. FAP9-S0456 exhibits higher tumor intensity and cleaner biodistribution than OTL38. In FIG. 80, imaging of MIA PaCa-2 tumors with a combination of FAP9-S0456 and OTL38 are shown. The results show good intensity and contrast but some non-specific uptake in the liver and stomach due to OTL38. FIG. 81 shows quantification of fluorescent intensity for the MIA PaCa-2 study. Tumor fluorescent intensity increased by 2.5-fold in cocktail compared to OTL38 alone and 1.5-fold compared to targeting FAP9 alone. The tumor-to-healthy tissue ratios were enhanced ~1.78-fold in the cocktail compared to OTL38 alone. Example 37 Cocktail Imaging in 4T1 Tumors A cocktail of FAP9-S0456 and OTL38 were administered to mice as described above. The mice in this example have 4T1 tumors. Doses of 5 nmol of FAP9-S0456 + 3 nmol of OTL38 were administered. Whole and ex vivo images acquired at 4 hours post-injection are shown in FIG.82. An excitation / emission of 745 / 810 nm was used. FIG. 83 presents quantification of mean fluorescent intensity for cocktail treated 4T1 tumor mice. In the cocktail imaging, the net tumor fluorescent intensity increased by 1.67-fold compared to targeting of OTL38 alone and ~2.4-fold compared to targeting FAP-S0456 alone. The tumor-to-healthy tissue ratios were enhanced over OTL38 alone by 1 to 3-fold. Tumor: muscle ratio of cocktail image vs OTL38 alone was 9.81 vs 3.1. Example 38 Cocktail Imaging in RENCA Tumors A cocktail of FAP9-S0456 and OTL38 were administered to mice as described above. The mice in this example have RENCA tumors. Doses of 5 nmol of FAP9-S0456 + 3 nmol of OTL38 were administered. Whole and ex vivo images acquired at 4 hours post-injection are shown in FIG. 84. An excitation / emission of 745 / 810 nm was used. FIG.85 presents quantification of mean fluorescent intensity for cocktail treated RENCA tumor mice. Fluorescent intensity increased by 2.2-fold compared to targeting folate alone and approximately 3-fold compared to targeting FAP-S0456 alone. The tumor-to-healthy tissue ratios were further enhanced in the cocktail images compared to OTL38 alone (1.5 to 2.3-fold). Tumor: muscle ratios cocktail vs. OTL38 was 6.1 vs.4.3. Example 39 Cocktail Imaging in CT26 Tumors A cocktail of FAP9-S0456 and OTL38 were administered to mice as described above. The mice in this example have CT26 tumors. Doses of 5 nmol of FAP9-S0456 + 3 nmol of OTL38 were administered. Whole and ex vivo images acquired at 4 hours post-injection are shown in FIG. 86. An excitation / emission of 745 / 810 nm was used. There is some non-specific uptake in the liver, which is carried over from OTL38. FIG. 87 presents quantification of mean fluorescent intensity for cocktail treated CT26 tumor mice. Fluorescent intensity increased by 2.0-fold compared to OTL38 alone and ~3.2-fold compared to FAP9-S0456 alone. The tumor-to-healthy tissue ratios were further enhanced ~1.5x in the cocktail images compared to OTL38 alone. Tumor: muscle ratios cocktail vs. OTL38 was 5.5 vs 3.6. Example 40 Cocktail Imaging in A549 Tumors A cocktail of FAP9-S0456 and OTL38 were administered to mice as described above. The mice in this example have A549 tumors. Doses of 5 nmol of FAP9-S0456 + 3 nmol of OTL38 were administered. Whole and ex vivo images acquired at 4 hours post-injection are shown in FIG. 88. An excitation / emission of 745 / 810 nm was used. There is some non-specific uptake in the liver, which is carried over from OTL38. FIG. 89 presents quantification of mean fluorescent intensity for cocktail treated A549 tumor mice. In the cocktail imaging, the net tumor fluorescent intensity increased by 1.6-fold compared to OTL38 and 1.6-fold compared to FAP9 alone. Tumor: muscle ratios cocktail vs OTL38 were 2.8 vs 1.6. Example 41 Cocktail Imaging in MDA-MB-231 Tumors A cocktail of FAP9-S0456 and OTL38 were administered to mice as described above. The mice in this example have MDA-MB-231 tumors. Doses of 5 nmol of FAP9-S0456 + 3 nmol of OTL38 were administered. Whole and ex vivo images acquired at 4 hours post-injection are shown in FIG.90. An excitation / emission of 745 / 810 nm was used. There is some non-specific uptake in the liver, which is carried over from OTL38. FIG. 91 presents quantification of mean fluorescent intensity for cocktail treated MDA- MB-231 tumor mice. The net tumor fluorescent intensity of the cocktail increases ~3.5x compared to FAP9 alone, but no significant improvement in tumor uptake was observed compared to mice injected with OTL38 alone. Example 42 Comparison of Cocktail versus Single Agent Tumor Fluorescence Intensity FIG.92 presents comparison of cocktail vs single agent tumor fluorescence intensities for 4T1, RENA, CT26, MIAPaCa2, A549, and MDA-MB-231 tumors. The results shown successful design and developed a novel FAPα-targeting ligand NIR conjugate (FAP9-S0456). The tumor- targeting ability and specificity of FAP9-S0456 were assessed in vivo across six tumor models. Optimal doses of FAP9-S0456 and OTL38 in six tumor models: 4T1, RENECA, CT26, MDA- MB-231, and A549 and MIA PaCa-2 were determined. In moderate FAP and folate-expressing tumor models (4T1, RENCA, CT26, MIAPaCa2 A549), cocktail imaging significantly enhanced tumor intensities (1.6 to 3-fold) and tumor-to-healthy tissue ratios (1- to 3-fold) compared to OTL38. In folate receptor-positive tumor models like MDA-MB-231, the increase in tumor fluorescent intensity was minimal or negligible. Example 43 Prophetic Synthetic Schemes Fig.47a shows the prophetic synthetic scheme and structure of FAP9 conjugates having different heterocyclic rings in the linker part. The prophetic structures in group B are synthesized using various chemical modifications from commercially available starting materials. Initially, the coupling of amine 9 with acid A yields the intermediate compound B. Subsequently, a Suzuki– Miyaura cross-coupling reaction between B and various substituted benzyl boronate derivatives produces the intermediates C. Further chemical modifications of these intermediates ultimately result in the final conjugates in group B series (Scheme 1). Fig.47b shows the prophetic synthetic scheme and structure of FAP9 conjugates having different aliphatic cyclic diamino rings in the linker part. The prophetic structure in group C are synthesized from a key fragment B. The Sonogashira cross coupling reaction of fragment B with different alkyne bromides (D), followed by catalytic hydrogenation yielded the intermediate E, which is further reaction with different cyclic diamine provide compounds F, then few functional group transformation on F results the group C conjugates (Scheme 2). Fig.47c shows the prophetic synthetic scheme and structure of FAP9 conjugates having a different combination of acyclic and cyclic linkers. The prophetic structures in group D are readily synthesized as shown in Scheme 3. Benzylic bromination of compound G using NBS / PPh3 and subsequent conversion of corresponding bromide to Wittig salt H by reaction with triphenyl phosphine. Then compound H is coupled with amine 9 provided the intermediate I. In another hand coupling of Ia or Ib with J provide the Ka and Kb respectively, which are Wittig reaction with intermediate I and hydrogenation of corresponding olefins yielded the N, few functional group transformation on N lead to the synthesis of group D conjugates (Scheme 3). Fig.47d shows the prophetic synthetic scheme and structure of FAP9 conjugates having different functionalized linkers. The prophetic structure in Group E is synthesized starting from intermediate compounds (Kb), which are reduced to their corresponding alcohols (Ma). The intermediate Ma is converted to corresponding bromide using NBS / PPh3 condition yielded the intermediate compound Mb, then alkylation of Mc with Mb in presence of NaH in DMF give the Md intermediate conjugate. Then the compound Md was treated with TFA, followed by coupling of resulted acid with amine 9 provided the intermediate Me. Finally, multiple functional group transformations on Me lead to the Group E conjugates, as depicted in Scheme 4. Fig.47e shows the prophetic synthetic scheme and structure of FAP9 conjugates having different functionalized linkers. Similarly, the Group F compounds are synthesized from the key intermediate Kb. Reductive amination of Kb with methylamine yields the compound Na, which undergoes subsequent alkylation and several transformations with appropriate starting material to produce the Group F conjugates, as shown in Scheme 5. Fig.47f and Fig. 47g show the prophetic synthetic scheme and structure of FAP9 conjugates having different bio reactive functionality in the linker part. The conjugates in Group E (Fig.46f) and Group F (Fig.46g) are synthesized by reacting to the appropriate intermediates from Scheme 3 and Scheme 4 with the key intermediate O. The synthesis of intermediate O was carried out following established literature protocols. Fig.47g shows the prophetic synthetic scheme and structure of FAP9 conjugates having different bio reactive functionality in the linker part. Example 44 (Fig.93) Synthesis of compound (18 and 29) To a solution of compound 14 (200.0 mg, 0.297mmol) in CH2Cl2(5 mL) in different reaction vials were added PyBOP (1.2 eq) + DIPEA (5.0eq) followed by respective amines (compound 16 (1.1 eq)), then continued the stirring at room temperature for an additional 2 hours. Reaction mixture was further diluted with water and extracted into CH2Cl2(2x30 mL), and combined organic extracts were evaporated under reduced pressure. Obtained crude compounds were purified by combi-flash using methanol+CH2Cl2 system to provide the respective compound 17. Then the Compound 17 (50 mg, 0.049 mmol) was dissolved in CH2Cl2(1.0 mL), TFA (1.0 mL) was added, and the mixture was allowed to stir for 6 hours, followed by the addition of TIPS (100 μL) and further stirring for one hour. Upon complete deprotection of the starting material as confirmed by LC-MS, the reaction mixture was concentrated under vacuum, diluted with minimal amount of dichloromethane, absorbed on celite, and subjected to reverse phase column chromatography using acetonitrile in 20 mM ammonium acetate (pH 5.0) as mobile phase. Lyophilization of the acquired fractions afforded compound 18 as white solid. Synthesis of compound (21) Compound 19 (1.0 mL, 11.054 mmol) was dissolved in CH3CN (8.0 mL) and cooled to 0°C, followed by dropwise addition of compound 20 dissolved in CH3CN (5.0 mL), and allowed to stir for 30 minutes at 0°C. 2-mercaptopyridine (0.9 eq) dissolved in CH3CN (20.0 mL) was added dropwise to the above reaction mixture and refluxed for two hours. The appearance of white precipitates in the reaction mixture confirmed the formation of the product. Following reflux, the reaction mixture was cooled to 0°C, stirred for 1h, and filtered, to afford compound 21 as white solid. Synthesis of compound (22) Compound 21 (500 mg, 2.66 mmol) was dissolved in CH2Cl2 (5.0 mL) along with TEA (1.0 eq) and added dropwise to a solution of triphosgene (0.33 eq) in CH2Cl2(5.0 mL) cooled at 0°C. The reaction mixture was stirred for 1.5h, followed by dropwise addition of a solution of hydroxybenzotriazole (1.0 eq) in CH2Cl2 (10.0 mL) and TEA (1.0 eq), and further allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with dichloromethane (50.0 mL), washed twice with distilled water (100 mL X 2) and brine (100 mL), the combined organic layer dried over anhydrous sodium sulfate and concentrated under vacuum. The crude extract was purified through column chromatography using ethyl acetate in hexane as mobile phase to obtain compound 22 as white solid. Synthesis of compounds (24, 26 and 28) To a stirred solution compound 22 in three different reaction vials (50 mg, 0.095 mmol) in DMF (1.0 mL) were added respective PI3K inhibitors (23, 25 and 27) (1.0 eq) and DIPEA (1.0 eq), stirred at room temperature for two hours. Completion of the reaction was determined by LC- MS. The reaction mixture was added with distilled water and dichloromethane, organic layer was collected and dried over anhydrous sodium sulfate, concentrated under vacuum, absorbed in celite and subjected to reverse phase chromatography using acetonitrile in 20 mM ammonium acetate (pH 7.0) as mobile phase. Lyophilization of the acquired fractions afforded activated PI3K inhibitors (24, 26 and 28) as white solids. Example 45 (Fig.93) Synthesis of FAP9-PI3K conjugate (29-31): To a stirred solution of compound 18 (50 mg, 0.144 mmol) in DMF (1.0 mL) in three different reaction vials were added activated PI3K inhibitors (24, 26 and 28) (1.0 eq) and DMAP (1.0 eq) and stirred at rt for 2h under argon atmosphere. Upon completion of the reactions as determined by LC-MS, the reaction mixtures were further diluted with water, followed by extracted into dichloromethane (2x20 mL), then the combined organic extracts dried over anhydrous sodium sulfate, concentrated under vacuum, absorbed in celite, and subjected to reverse phase chromatography using acetonitrile in 20 mM ammonium acetate (pH 7.0) as mobile phase. Lyophilization of the acquired fractions provided the desired final conjugates (29-31) as white solids. Example 46 (Fig.94) Synthesis of compound (34) For the synthesis and purification of activated TGF-β compounds 36 and FAP9- TGF-β conjugates (33 and 34) followed the same experimental conditions as described in the scheme-1- 3 using appropriate starting materials. Example 47 (Fig.95) Synthesis of FAP9-TGFβ conjugate (37-38): To a stirred solution of compound 18 (50 mg, 0.144 mmol) or 34 (50 mg, 0.054 mmol) in DMF (1.0 mL) in two different reaction vials were added activated TGFβ inhibitors (36) (1.0 eq) and DMAP (1.0 eq) and stirred at room temperature for two hours under argon atmosphere. Upon completion of the reactions as determined by LC-MS, the reaction mixtures were further diluted with water, followed by extracted into dichloromethane (2x20 mL), then the combined organic extracts dried over anhydrous sodium sulfate, concentrated under vacuum, absorbed in celite, and subjected to reverse phase chromatography using acetonitrile in 20 mM ammonium acetate (pH 7.0) as mobile phase. Lyophilization of the acquired fractions provided the desired final conjugates (37 and 38) as white solids. Example 48 (Figs.96-97) To a stirred solution of compound 23 (1.0 eq) in DMF (1 mL / 100mg) was added NaH ( 2.0 eq), followed by tert-butyl (2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethyl)carbamate (1.0 eq),then stirred the reaction mixture at room temperature for 2-3 hours, progress of the reaction was monitored by LC-MS. Reaction mixture was diluted with water and extracted into ethyl acetate, then evaporate and obtained crude residue was purified by HPLC provided desired compound 39. Then compound 39 was dissolved in CH2Cl2, TFA was added, and the mixture was stirred at room temperature. The reaction mixture was evaporated under reduced pressure, and the obtained crude compound was reacted with acid (4) using PyBOP / DIPEA in CH2Cl2to provide the compound 40 as white solid. Fig.97 shows the synthesis of conjugate (41) with a non-cleavable linker. Example 49 (Fig.98) To a stirred solution of acid (14) in dichloromethane was added PyBOP / DIPEA followed by Val-Cit linkers (44), provided the couple product 45 and which was further reacted with 4- nitrophenyl carbonochloridate gave the activated compound 46. Then the reaction of compound 46 with different PI3K inhibitors in DMF / DIPEA condition provided their corresponding FAP9- PI3K conjugates (47-49) with cathepsin cleavable linkers. Example 50 (Fig.99) Similarly, the FAP9-TGFβ conjugates (50-53) were synthesized by reaction of compound 46 with different TGFβ inhibitors. Example 51 (Fig.102) Fig.102 presents a synthetic scheme to attach various drug moieties to FAB9 moieties of the instant disclosure. Compound 22 and Compound 46 are illustrated as attaching the drug (D) to the compound. While any suitable drug may be utilized, the following are examples of suitable drugs.

[0047] Mice bearing various tumors, such as 4T1, RENCA, CT26, MDA-MB-231, A549, and PANC-1, are injected with a cocktail mixture containing 5 nmol of FAP9-S0456, 2 nmol of OTL38, and 2 nmol of a CA-IX targeting ligand. Whole-body and ex vivo biodistribution imaging are acquired at 4 hours post-injection. Quantitative analysis of fluorescent intensity in tumors and healthy tissues will demonstrate that the cocktail mixture results in enhanced tumor intensity and an improved tumor-to-healthy tissue ratio compared to single-agent treatments The term “about” as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range. Values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range were explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise. In this document, the terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated. In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings and subheadings is solely for ease of reference and is not intended to limit any disclosure made in one section to that section only; rather, any disclosure made under one section heading or subheading is intended to constitute a disclosure under each and every other section heading or subheading. Various modifications and variations of the described compositions, methods, and uses of the technology will be apparent to those skilled in the art without departing from the scope and spirit of the technology as described. Although the technology has been described in connection with specific exemplary embodiments, the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the art are intended to be within the scope of the following claims. The terms and expressions which have been employed, are used as terms of description and not of limitation. In this regard, where certain terms are defined and are described or discussed elsewhere, the definitions and all descriptions and discussions are intended to be attributed to such terms. There also is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof. Further, all publications and patents mentioned herein are incorporated by reference in their entireties for all purposes. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls. Enumerated Embodiments (EE) The following list of enumerated embodiments presents claims with multiply dependent claims depending from multiply dependent claims for presentation in those jurisdictions where such dependencies are allowed as well as additional claims, which may be presented during the examination of the application or any divisional or continuation thereof. EE 1. A conjugate of formula I or formula II: wherein A is a ligand having a structure of formula IX or formula X: RR R57 R65R RR6 RR4R7R4 and a molecular weight below 10,000; L is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or to A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio- sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; C is a pharmacokinetic (PK) extender; and wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- aromat icyclic heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the functionalized 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic a primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13is selected from the group of substituents consisting of -H, -D, Cl-Cl0alkyl, -C3-Cl0cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20alkyl aryl is: is selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which is optionally substituted, and R14, R15, R16, and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted; or R13is and R22 are independently selected from the group of substituents consisting of -H, -D, -OMe, -C1-C3 alkyl, benzyl (Ph-CH2-), substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted; and stereoisomers, pharmaceutically acceptable salts, and hydrates thereof. EE 2. The conjugate of EE 1, wherein A has the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:

[0048]

[0049] where R1 is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6alkyl, -O-C1-6alkyl, -S-C1-6alkyl, -Cl-Cl0alkyl, -C3-Cl0cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, - D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26 are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted. EE 3. The conjugate of EE 1 or 2, wherein R13is independently selected from the group of substituents consisting of EE 4. The conjugate of EE 1 having the formula A-L-B, wherein A is a fibroblast activation protein alpha (FAP^) targeting ligand having a structure of formula (I) or (II): . EE 5. The conjugate of EE 4, wherein B is selected from:

[0050] . EE 6. The conjugate of EE 4, wherein B comprises optical imaging agent S0456 which has the structure: HO3S SO3H , wherein R32is

[0051] or EE 7. The conjugate of any one of EEs 1-3, wherein at least one of B, B’ and B” comprises (i) a metal chelating group optionally bound to a metal or a group covalently bound to an isotope, wherein said metal or isotope can be used for radio-imaging, radiotherapy, or magnetic resonance imaging, (ii) a fluorescent imaging agent, (iii) an optical imaging agent, (iv) a photosensitizer, (v) a radiosensitizer, (vi) a chemo-sensitizer, or (vii) an immunotherapeutic agent. EE 8. The conjugate of any one of EEs 1-3, wherein the PK extender is an albumin- binding ligand, a plasma protein-binding ligand, a hapten, or an internalization-inducing peptide. EE 9. The conjugate of any one of EEs 1-8, wherein L comprises one or more of an amino acid, a polyethylene glycol (PEG) monomer, a PEG oligomer, a PEG polymer, a heterocycle, or any combination of two or more thereof. EE 10. The conjugate of any one of EEs 1-8, wherein L comprises an oligomer of one or more peptidoglycans, glycans, anions, heterocycles, or any combination of two or more thereof. EE 11. The conjugate of any one of EEs 1-8, wherein L comprises at least one diamino butyric acid group, a substituted benzene group, a lysine group, a 2,3-diaminopropionic acid group, a tyrosine group, a glutamic acid group, a cysteine group, or any combination of two or more thereof. EE 12. The conjugate of any one of EEs 1-8, wherein L comprises an ether, a thioether, a tertiary amine, a C1-6 alkyl, piperazine, piperidine, a bicycloheptane, a substituted benzene, or a combination of two or more thereof. EE 13. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 14. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 15. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 16. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 18. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula:

[0052] EE 19. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 20. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula:

[0053] . EE 21. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: EE 22. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: . EE 23. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: . EE 24. The conjugate of any one of EEs 1-8, wherein L comprises a reductively cleavable linker. EE 25. The conjugate of any one of EEs 1-8, wherein L comprises an oxidatively cleavable linker. EE 26. The conjugate of any one of EEs 1-8, wherein L comprises an oxime ester. EE 27. The conjugate of any one of EEs 1-8, wherein L comprises a hydrazone. EE 28. The conjugate of any one of EEs 1-8, wherein L comprises an enzyme-cleavable linker. EE 29. The conjugate of any one of EEs 1-8, wherein L comprises a PEGn, and n = 0-36. EE 30. The conjugate of any one of EEs 1-8, wherein L comprises a peptide. EE 31. The conjugate of any one of EEs 1-8, wherein L comprises a peptidoglycan. EE 32. The conjugate of any one of EEs 1-8, wherein L is: . EE 33. The conjugate of any one of EEs 1-8, wherein L is a linker selected from the group consisting of pegylated-, alkyl-, sugar-, and peptide-based dual linkers. EE 34. The conjugate of any one of EEs 1-8, wherein L is a non-releasable linker. EE 35. The conjugate of any one of EEs 1-8, wherein L is covalently bonded to A and B of formula (I) or A, B and C of formula (II) or A, B’, and B” of formula (III). EE 36. The conjugate of any one of EEs 1-8, wherein L comprises a moiety of the formula: S OOO O OOS O OCO2H. EE 37. The conjugate of any one of EEs 1-8, wherein L comprises a moiety selected from: COOH COOH 28 can be optionally substituted; and z is an integer from 1 to 8. EE 38. The conjugate of any one of EEs 1-8, wherein L comprises:

[0054] EE 39. The conjugate of any one of EEs 1-8, wherein L comprises: each of R29a, R29b, R30a, and R30b is independently H or C1- can EE 40. The conjugate of any one of EEs 1-39, wherein at least one of B, B’ and B” comprises an optical dye. EE 41. The conjugate of EE 40, wherein the optical dye is a fluorescent dye. EE 42. The conjugate of EE 41, wherein the fluorescent dye is or comprises carbocyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, polymethine, coumarine, rhodamine, xanthene, fluorescein, borondipyrromethane (BODIPY), CyS, CyS.S, Cy7, VivoTag-680, VivoTag-S680, VivoTag-S7S0, AlexaFluor660, AlexaFluor680, AlexaFluor700, AlexaFluor7S0, 10 AlexaFluor790, Dy677, Dy676, Dy682, Dy7S2, Dy780, DyLightS47, Dylight647, HiLyte Fluor 647, HiLyte Fluor 680, HiLyte Fluor 7S0, IRDye 800CW, IRDye 800RS, IRDye 700DX, ADS780WS, ADS830WS, or ADS832WS. EE 43. The conjugate of EE 41, wherein the fluorescent dye is or comprises a structure selected from:

[0055] . EE 44. The conjugate of EE 41, wherein the fluorescent dye has a peak emission in NIR-ow (1000-1700 nm). EE 45. The conjugate of EE 41, wherein the fluorescent dye is selected from:

[0056]

[0057] E . e conjugae o any one o s - an - , weren a eas one of B, B’ and B” comprises a photosensitizer selected from:

[0058] . C N EE 47. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” comprises a chelating group selected from DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) or a derivative thereof; S-2-(4-isothiocyanatobenzyl)-1,4,7,10- tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) or derivative thereof; 2-S-(4- isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) or a derivative thereof; [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2- diamine-pentaacetic acid (p-SCN-Bn-CHX-A”-DTPA) or a derivative thereof; TETA (1,4,8,11- tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) or a derivative thereof; SarAr (1-N-(4- aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine or a derivative thereof; NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) or a derivative thereof; NETA (4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl) acetic acid or a derivative thereof; TRAP (1,4,7-triazacyclononane-1,4,7-tris[methyl(2- carboxyethyl)phosphinic acid) or a derivative thereof; HBED (N,N0-bis(2-hydroxybenzyl)- ethylenediamine-N,N0-diacetic acid) or a derivative thereof; 2,3-HOPO (3-hydroxypyridin-2- one) or a derivative thereof; PCTA (3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13- triene-3,6,9,-triacetic acid) or a derivative thereof; DFO (desferrioxamine) or a derivative thereof; DTPA (diethylenetriaminepentaacetic acid) or a derivative thereof; OCTAPA (N,N0- bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; H2-MACROPA (N,N'-bis[(6-carboxy-2-pyridipmethyl]-4,13-diaza-18-crown-6) or a derivative thereof; H2dedpa (1,2-[[carboxy)-pyridin-2-yl]-methylamino]ethane or a derivative thereof; and EC20-head comprising β-l-diaminopropionic acid, aspartic acid, and cysteine, wherein the chelating group optionally chelates a metal. EE 48. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” comprises a radioisotope / radionuclide for radio-imaging, radiotherapy, or magnetic resonance imaging (MRI). EE 49. The conjugate of EE 48, wherein the radioisotope / radionuclide is selected from the group consisting of177Lu,90Y,211At,225Ac,161Tb,18F,32P,44Sc,47Sc,52Mn,55Co,64Cu,67Cu,67Ga,68Ga,86Y,89Sr,89Zr,99mTc,111In,114mIn,117mSn,124I,125I,131I,149Tb,153Sm,152Tb,155Tb,169Er,186Re,188Re,212Pb,212Bi,213Bi,223Ra,224Ra,225Ab,161Tb, and227Th. EE 50. The conjugate of EE 48, wherein the radioisotope / radionuclide is selected from the group consisting of11C,13C,13N,15O,60Co, and123I. EE 51. The conjugate of EE 48, wherein at least one of B, B’ and B” is or comprises a group selected from: group consisting of 18p,124I,125I,131I, and2llAt; each R and R' is independently selected from -H, -D, -C1-C3 alkyl, benzyls and substituted benzyls; and each n is independently an integer selected from the group consisting of 0,1,2,3,4,5,6,7,8, 9,10,11,12,13, 14, 15, 16, 17, 18, 19, and 20. EE 52. The conjugate of EE 48, wherein at least one of B, B’ and B” is or comprises a radiolabeled prosthetic group selected from the group consisting of: EE 53. The conjugate of EE 48, wherein at least one of B, B’ and B” comprises a chelating agent selected from: EE 54. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” comprises a nuclide for positron emission tomography (PET) or single-photon emission computed tomography (SPECT). EE 55. The conjugate of EE 54, wherein the nuclide is selected from the group consisting of99mTc,111In,18F,68Ga,124I,125I,131I, and64Cu. EE 56. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” is an anti-tumor agent selected from: EE 57. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” is a radiosensitizer selected from:

[0059] . EE 58. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” is a radiosensitizer selected from a topoisomerase inhibitor (e.g., camptothecin, topotecan), an hypoxia-activated anthraquinone, and an alkylating agents (e.g., temozolomide). EE 59. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” is DNA repair inhibitor (e.g., poly (ADP ribose) polymerase inhibitors (AG14,361, Fuzuloparib, Olaparib, Pamiparib (BGB-290), and Rucaparib) or a PRMT5 inhibitor (e.g., JNJ- 64619178) or DNA-PKc inhibitors (AZD7648, Peposertib (M3814) or ATM inhibitors (AZD0156, AZD1390) or dual DNA-PKc and ATM inhibitor (XRD-0394). EE 60. The conjugate of any one of EEs 1-3 and 7-39, wherein at least one of B, B’ and B” comprises a chemotherapeutic agent. EE 61. The conjugate of EE 60, wherein the chemotherapeutic agent is a Wnt / ^-catenin inhibitor. EE 62. The conjugate of EE 60, wherein the chemotherapeutic agent is a kinase inhibitor for VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, or PDGFR. EE 63. The conjugate of EE 60, wherein the chemotherapeutic agent is selected from: . EE 64. The conjugate of EE 60, wherein the chemotherapeutic agent is an inhibitor of focal adhesion kinase (FAK) or Rho-associated protein kinase (ROCK). EE 65. The conjugate of EE 60, wherein the chemotherapeutic agent is an inhibitor of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). EE 66. The conjugate of EE 60, wherein the chemotherapeutic agent is an agonist of a toll-like receptor. EE 67. The conjugate of any one of EEs 1-39, wherein B comprises a structure selected from:

[0060] . EE 68. The conjugate of any one of EEs 1-39, wherein B, B’, and B” are each independently a kinase inhibitor for vascular endothelial growth factor receptor (VEGFR), such as an inhibitor for VEGFR1, VEGFR2, or VEGFR3, fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), a platelet-derived growth factor receptor (PDGFR), a phosphatidylinositol-3-kinase (PI3k) inhibitor, a dual inhibitor of the PI3k / mTOR signaling pathway, or a transforming growth factor β (TGFβ) inhibitor.

[0061] EE 69. The conjugate of any one of EEs 1-39, wherein B, B’, and B” are independently from the group consisting of: . EE 71. The conjugate of EE 68, wherein the PI3k inhibitor comprises the structure: . EE 72. The conjugate of EE 68, wherein the PI3K inhibitor comprises the structure. N N X A Z -CO-, EE 73. The conjugate of EE 68, wherein TGFβ inhibitor has the structure: . EE 74. The conjugate of EE 68, wherein ROCK inhibitor can have the structure:

[0062] EE 75. The conjugate of any one of EEs 1-74, wherein C is an albumin binding ligand, a disulfide-stabilized protein scaffold comprising albumin binding domain 035 (ABD035), albumin binding domain Con (i.e., a peptide of a three-helix bundle 45 amino acids in length (ABDCon)), a designed ankyrin repeat protein (DARPin), a disulfide-stabilized Fv fragment (dsFv) of an anti-albumin antibody (e.g., CA645), a nanobody that complexes with human serum albumin (HSA), or a variable new antigen receptor (VNAR) (e.g., E06). EE 76. The conjugate of any one of EEs 1-74, wherein C is or comprises: . EE 77. The conjugate of any one of EEs 1-74, wherein C is or comprises:

[0063] wherein, as applicable: each of R12-19 (where applicable) is independently selected from -H, -C1-C6 alkyl, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, -C(O)alkyl, -C(O)aryl-, -C=C-C(O)aryl, -C=C-S(O)2aryl, -CO2H, -SO3H, -SO2NH2, -PO3H2, and -SO2F; and each of R20 and R21 is independently selected from -H, -C1-C6 alkyl, -F, -Cl, -Br, -I, -O-C1-6alkyl, -CN, -CHO, -B(OH)2, -C=C-C(O)aryl, -C=C-S(O)2aryl, -CO2H, -SO3H, -SO2NH2, , -PO3H2, -SO2F, and CF3. EE 78. The conjugate of any one of EEs 1-74, wherein C is or comprises:

[0064] . EE 79. The conjugate of any one of EEs 1-74, wherein C is or comprises: I . EE 80. The conjugate of any one of EEs 1-77, wherein C is or comprises: HO3SSO3H EE 81. The conjugate of any one of EEs 1-74, wherein C comprises (e.g., a radical of) (PEG)n, wherein n is an integer 0 to 32, a peptide, a peptidoglycan, or a saccharide. EE 82. The conjugate of any one of EEs 1-74, wherein C comprises . EE 83. The conjugate of any one of EEs 1-74, wherein C is a hapten bound by an autologous antibody. EE 84. The conjugate of any one of EEs 1-74, wherein C is a hapten selected from rhamnose, an α-galactosyl moiety, a dinitrophenyl (DNP) moiety, and a trinitrophenyl (TNP) moiety. EE 85. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure:

[0065] EE 86. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure:

[0066] Me wherein n is an integer from 1-5. EE 87. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure:

[0067] EE 88. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure:

[0068] therapy, or MRI. EE 89. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure:

[0069] radiotherapy, or MRI. EE 90. The conjugate of EE 1, wherein the conjugate of formula (I) has the following structure: or MRI. EE 91. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure:

[0070] ng, radiotherapy, or magnetic resonance imaging. EE 92. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure: radiotherapy, or MRI. EE 93. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure:

[0071] following structure:

[0072] radiotherapy, or magnetic resonance imaging. EE 95. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure:

[0073] magnetic resonance imaging. EE 96. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure: radiotherapy, or magnetic resonance imaging. EE 97. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure: magnetic resonance imaging. EE 98. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure: or magnetic resonance imaging. EE 99. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure: or magnetic resonance imaging. EE 100. The conjugate of EE 1, wherein the conjugate of formula (II) has the following structure:

[0074] . EE 101. The conjugate of EE 1, wherein A can have the following structure: . EE 102. The conjugate of EE 1, wherein A can have the following structure:

[0075] . EE 103. The conjugate of EE 1, wherein A can have the following structure: . EE 104. The conjugate of EE 1, wherein A can have the following structure:

[0076] . EE 105. The conjugate of EE 1, wherein the conjugate of formula (I) can have the following structure: . EE 106. The conjugate of EE 1, which has the structure: . EE 107. The conjugate of EE 1, which has the structure:

[0077] . EE 108. The conjugate of EE 1, which has the structure:

[0078] . EE 109. The conjugate of EE 1, which has the structure:

[0079] EE 110. The conjugate of EE 1, which has the structure:

[0080] . EE 111. The conjugate of EE 1, wherein A has the structure of formula: EE 112. The conjugate of EE 1 or EE 111, wherein R13 is . The conjugate of any one of EE 1, EE 111 and EE 112, wherein L comprises - (O−CH2−CH2)n- where n is an integer from 1-11. EE 114. The conjugate of any one of EE 1 and EE 111-113, wherein B comprises an optical imaging agent. EE 115. The conjugate of EE 114, wherein B comprises optical imaging agent S0456 which has the structure:

[0081] ;

[0082] or EE 116. The conjugate of any one of EE 1 and EE 111-115, wherein C is an albumin- binding ligand. EE 117. A pharmaceutical composition comprising a conjugate of any one of EEs 1-116 and a pharmaceutically acceptable carrier. EE 118. A method of imaging cancer or fibrosis in a patient, which method comprises administering to the patient a conjugate of any one of EEs 1-116 and imaging the cancer or the fibrosis in the patient. EE 119. A method of treating cancer or inflammation in a patient, which method comprises administering to the patient an effective amount of a conjugate of anyone of ees 1-116, whereupon the patient is treated for cancer or inflammation. EE 120. The conjugate of any one of EEs 1-116 for use in a method of treating cancer or inflammation. EE 121. The conjugate of any one of EEs 1-116 for use in imaging of cancer or fibrosis in a patient. EE 122. A method of imaging cancer or fibrosis in a patient, which method comprises (i) administering to the patent a combination of near infrared (NIR) imaging agents comprising (a)

[0083] nd (ii) imaging the cancer or the fibrosis in the patient. EE 123. The method of EE 122, wherein the dose of NIR imaging agents is about 2 to about 5 nmol. EE 124. A ligand that targets fibroblast activation protein alpha (FAP^), wherein the ligand has the structure of formula (IX) or formula (X): R7R6R5R4 R7R6R5Rand a wherein: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- aromatic, mono- or bicyclic heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the functionalized 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclic heterocycle, a alkyl primary amine, a alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1 is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6alkyl, -O-C1-6alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11 are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; and R13 is selected from the group of substituents consisting of -H, -D, Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20alkyl aryl is: selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which is optionally substituted, and R14, R15, R16, and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted; or R13 is and R22 are independently selected from the group of - - -OMe, -C1-C3alkyl, benzyl (Ph-CH2-), substituted / functionalized benzyl, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted, and R14, R15, R16 and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3alkyl, -Cl-C3alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, and any substituent comprising at least two atoms can be optionally independently substituted. EE 125. The ligand of EE 124, which has the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:

[0084]

[0085] where R1is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, - D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26 are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted. EE 126. The ligand of EE 124 or 125, wherein R13is independently selected from the group of substituents consisting of EE 127. A chelated complex of a compound represented by a formula selected from the group consisting of

[0086] . EE 128. A chelated complex of a compound represented by a formula selected from the group consisting of: . EE 129. A chelated complex of a compound represented by a formula selected from the group consisting of: . EE 130. A chelated complex of a compound represented by a formula selected from the group consisting of:

[0087] F F O OMe N

[0088] .

Claims

WHAT IS CLAIMED IS:

1. A conjugate of formula I or formula II: A-L-B (I) , , or wherein A is a ligand having a structure offormula IX or RR R57 R65R4 R7R6 RR4O R3O R8 3L is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and an optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio- sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; and C is a pharmacokinetic (PK) extender; and wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non-heterocycle, which can optionally comprise 1-3 heteroatoms independently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the5- to 10-membered, N-containing,aromatic or non-aromatic, mono- or bicyclic heterocycle, a primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1 is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6 and R7 are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6alkyl, -O-C1-6alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally independently substituted; R9, R10, and R11 are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12 is selected from the group of substituents consisting of -H, -D, -F, -C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R13 is selected from the group of substituents consisting of -H, -D, Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally independently substituted and the aryl in C7-C20alkyl aryl is:selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which is optionally substituted, and R14, R15, R16, and R17are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12,wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted; or R13 is are independently selected from the group of substituents- - - - alkyl, benzyl (Ph-CH2-), and substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally independently substituted, and R14, R15, R16and R17are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally substituted; and stereoisomers, pharmaceutically acceptable salts, and hydrates thereof.

2. The conjugate of claim 1, wherein A has the structure of formula III:

3. The conjugagate of claim 1 or claim 2, wherein R13 is .of any one of claims 1-3, wherein L comprises -(O−CH2−CH2)n- where n is an integer from 1-11.

5. The conjugate of any one of claims 1-4, wherein B, B’, or B’ comprises an optical imaging agent.

6. The conjugate of claim 5, wherein B, B’, or B” comprises optical imaging agent S0456 which has the structure: ;or 7. The conjugate of any one of claims 1-6, wherein C is an albumin-binding ligand.

8. The conjugate of claim 1 comprising the structure:.

9. A method of imaging cancer or fibrosis in a patient, which method comprises administering to the patient a conjugate of anyone of claims 1-8 and imaging the cancer or the fibrosis in the patient.

10. A method of treating cancer or inflammation in a patient comprising administering to the patient an effective amount of a conjugate of anyone of claims 1-8, whereupon the patient is treated for cancer or inflammation.

11. The conjugate of any one of claims 1-8 for use in a method of treating cancer or inflammation.

12. The conjugate of any one of claims 1-8 for use in imaging of cancer or fibrosis in a patient.

13. A method of imaging cancer or fibrosis in a patient, which method comprises (i) administering to the patent a combination of near infrared (NIR) imaging agents comprising (a)(ii) imaging the cancer or the fibrosis in the patient.

14. The method of claim 13, wherein the dose of NIR imaging agents is about 2 to about 5 nmol.

15. The conjugate of any one of claims 1 and 4-7, wherein A has the structures of formulae III, formulae IV, formulae V, formulae VI, formulae VII, or formulae VIII:where R1is selected from the group of substituents consisting of -F, -Cl, -Br, -I, -OH, -CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, -adamantyl, -aryl and -C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6and R7are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8 is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R12and R13are independently selected from the group of substituents consisting of -H, -D, -F, - C1-C6 alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; and R23-R26are independently selected from group of substituents consisting of -H, -OH, -F, -Cl, -Br, -I, -CF3, -NO2, -SO3H, -SO2NH2, -NH2, -N3, -NH=NH2, -C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6alkyl, and the structure -X-L-B or -X-L(BC), wherein X is O, S, -NH, -NCH3,or -CH2, wherein any substituent comprising at least two atoms can be optionally independently substituted.

16. The conjugate of any one of claims 1-7 and 15, wherein R13is selected from the group of substituents consisting ofO O O O O O OOOFO17. The conjugate of claim 1 having the formula A-L-B, wherein A is a fibroblast activation protein alpha (FAP^) targeting ligand having a structure of formula (I) or (II): .

18. The conjugate of claim 17, wherein B is selected from:.

19. The conjugate of claim 17, wherein B comprises optical imaging agent S0456, which has the structure:;or 20. The conjugate of any one of claims 1-7 and 15-19, wherein the PK extender is an albumin- binding ligand, a plasma protein-binding ligand, a hapten, or an internalization-inducing peptide.

21. The conjugate of any one of claims 1-4, 7, and 15-20, wherein at least one of B, B’ and B” comprises a fluorescent dye.

22. The conjugate of any one of claims 1-4, 7, and 15-21, wherein at least one of B, B’ and B” comprises a radioisotope / radionuclide for radio-imaging, radiotherapy, or magnetic resonance imaging (MRI).

23. The conjugate of claim 22, wherein the radioisotope / radionuclide is selected from the group consisting of177Lu,90Y,211At,225Ac,161Tb,18F,32P,44Sc,47Sc,52Mn,55Co,64Cu,67Cu,67Ga,68Ga,86Y,89Sr,89Zr,99mTc,111In,114mIn,117mSn,124I,125I,131I,149Tb,153Sm,152Tb,155Tb,169Er,186Re,188Re,212Pb,212Bi,213Bi,223Ra,224Ra,225Ac,161Tb, and227Th.

24. The conjugate of claim 22, wherein the radioisotope / radionuclide is selected from the group consisting of11C,13C,13N,15O,60Co, and123I.

25. The conjugate of claim 22, wherein at least one of B, B’ and B” is or comprises a radiolabeled prosthetic group selected from the group consisting of:

26. The conjugate of any one of claims 1-4, 7, and 15-21, wherein at least one of B, B’ and B” comprises a chelating group selected from DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) or a derivative thereof; S-2-(4-isothiocyanatobenzyl)-1,4,7,10- tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) or derivative thereof; 2-S-(4- isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) or a derivative thereof; [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2- diamine-pentaacetic acid (p-SCN-Bn-CHX-A”-DTPA) or a derivative thereof; TETA (1,4,8,11- tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) or a derivative thereof; SarAr (1-N-(4- aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine or a derivative thereof; NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) or a derivative thereof; NETA (4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl) acetic acid or a derivative thereof; TRAP (1,4,7-triazacyclononane-1,4,7-tris[methyl(2- carboxyethyl)phosphinic acid) or a derivative thereof; HBED (N,N0-bis(2-hydroxybenzyl)- ethylenediamine-N,N0-diacetic acid) or a derivative thereof; 2,3-HOPO (3-hydroxypyridin-2- one) or a derivative thereof; PCTA (3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13- triene-3,6,9,-triacetic acid) or a derivative thereof; DFO (desferrioxamine) or a derivative thereof; DTPA (diethylenetriaminepentaacetic acid) or a derivative thereof; OCTAPA (N,N0- bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N0-diacetic acid) or a derivative thereof; H2-MACROPA (N,N'-bis[(6-carboxy-2-pyridipmethyl]-4,13-diaza-18-crown-6) or a derivative thereof; H2dedpa (1,2-[[carboxy)-pyridin-2-yl]-methylamino]ethane or a derivative thereof; andEC20-head comprising β-l-diaminopropionic acid, aspartic acid, and cysteine, wherein the chelating group optionally chelates a metal.

27. The conjugate of any one of claims 1-4, 7, and 15-21, wherein at least one of B, B’ and B” comprises a nuclide for positron emission tomography (PET) or single-photon emission computed tomography (SPECT).

28. The conjugate of any one of claims 1-3, 5-7, and 15-27, wherein L comprises one or more of an amino acid, a polyethylene glycol (PEG) monomer, a PEG oligomer, a PEG polymer, a polylactone, a polymethylmethacrylate, a polyoxymethylene, a heterocycle, or any combination of two or more thereof.

29. A pharmaceutical composition comprising a conjugate of any one of claims 1-8 and 15-28 and a pharmaceutically acceptable carrier.

30. A ligand that targets fibroblast activation protein alpha (FAP^), wherein the ligand has the structure of formula (IX) or formula (X): RR57 R6 R4 R7R6R5RL is a bi-functionalized linker, which binds A and B, or L is a tri-functionalized linker, which binds A, B and C or A, B’, and B”; B, B’ and B” are independently (i) an imaging agent selected from a radio-imaging agent, a fluorescent imaging agent, and optical imaging agent, (ii) an antitumor agent selected from a chemotherapeutic agent and a radiotherapeutic agent, (iii) an antifibrotic agent, (iv) a radio-sensitizing agent, (v) a chemo-sensitizing agent, (vi) a photo-sensitizing agent, and / or (vii) an immunotherapeutic agent; C is a pharmacokinetic (PK) extender; and wherein, in formulae IX and X: is a functionalized, 5- to 10-membered, N-containing, aromatic or non- heterocycle, which can optionally comprise 1-3 heteroatomsindependently selected from O, N, and S, and indicates the point of attachment of A to L or A attaches to L via any carbon atom of the 5- to 10-membered, N-containing, aromatic or non-aromatic, mono- or bicyclica primary amine, an alkyl primary amine, a secondary amine, an alkyl secondary amine, a functionalized alkyl, or a functionalized cycloalkyl; R1is selected from the group of substituents consisting of F, Cl, Br, I, OH, CF3, -NO2, -NH2, -N-C1-6 alkyl, -O-C1-6 alkyl, -S-C1-6 alkyl, Cl-Cl0 alkyl, C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted; R2, R3, R4, R5, R6and R7are independently selected from the group of substituents consisting of -H, -D, - OH, -F, -Cl, -Br, -I, -C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R8is selected from the group of substituents consisting of -H, -D, -OH, =CH2, -CH3, -CH2CH3, -C(H)(CH3)2, -C(CH3)3, and -CH2Ph, wherein any substituent comprising at least two atoms can be optionally substituted; R9, R10, and R11are independently selected from group of substituents consisting of -H, -D, -OH, -F, -Cl, -Br, -I, -NO2, -SO3H, -SO2NH2, -N3, -NH=NH, -N-C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, wherein any substituent comprising at least two atoms can be optionally independently substituted; R12is selected from the group of substituents consisting of -H, -D, -F, -C1-C6alkyl, -C(O)CH3, and -Cl-Cl0 alkyl, wherein any substituent comprising at least two atoms can be optionally substituted; andR13 is selected from the group of substituents consisting of -H, -D, Cl-Cl0 alkyl, -C3-Cl0 cycloalkyl, adamantyl, aryl, and C7-C20 alkyl aryl, wherein any substituent comprising at least two atoms can be optionally substituted and the aryl in C7-C20alkyl aryl is: selected from the group consisting of -H, -D, -halo, and Cl-C4 alkyl, which isand R14, R15, R16, and R17are independently selected from the group of substituents consisting of -H, -D, -halo, -Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12 is as defined above, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted; or R13 isare independently selected from the group of substituents consisting of -H, -D, -OMe, -C1-C3 alkyl, benzyl (Ph-CH2-), substituted / functionalized benzyls, the dashed line indicates the point of attachment to the nitrogen of formula IX or formula X, and any substituent comprising at least two atoms can be optionally substituted, and R14, R15, R16and R17 are independently selected from the group of substituents consisting of -H, -D, -halo, -OMe, - Cl-C3 alkyl, -Cl-C3 alkoxy, -CF3, and -C(=O)OR12, wherein R12is as defined above, and any substituent comprising at least two atoms can be optionally substituted.

Images