Integrin-targeted radiotheranostic platforms

Abstract

The present invention provides a carrier platform functionalized with a chelating agent. The carrier platform has a Formula I as follows: ITP- Pu According to Formula I, ITP represents an integrin-targeting peptide that comprises cRGD, linear RGD or iRGD, MBD represents a metal-ion binding domain comprising a bifunctional chelating agent and Pu is a polymeric unit. The present invention provides a novel radiotheranostic platform suitable for use as diagnostic or imaging agents or therapeutic agent.

Description

[0001] INTEGRIN-TARGETED RADIOTHERANOSTIC PLATFORMS

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to targeted agent delivery systems. More specifically, the invention concerns carrier platforms functionalized with chelating agents and integrin-targeting peptides, such as cRGD, linear RGD, or iRGD. The invention further relates to a conjugate comprising at least one targeting moiety and bifunctional chelating agent suitable for radiolabeling or coordination with metal ions, thus providing a multifunctional platform for diagnostic or therapeutic applications. The present invention also relates to a radioisotope-labeled agent that can be used as a radiotheranostic agent in combination with nuclear medicine diagnosis and nuclear medicine therapy. The present disclosure relates generally to the field of disease imaging and therapy. In one embodiment, the present disclosure provides radiotheranostic agents that target integrin expressed on cells of solid tumor cells.

[0004] BACKROUND OF THE INVENTION

[0005] Cancer continues to be a major cause of mortality worldwide, with many existing treatments inflicting substantial harm on healthy tissues, leading to significant side effects and reduced effectiveness. In recent years, research on polymer materials as drug carriers has gained significant attention, underscoring the growing importance of polymeric nanomedicines. The ability of these carriers to efficiently reach disease sites is essential for their effective application in drug delivery systems. By conjugating chemotherapy drugs to polymer backbones, these systems can improve drug solubility, stability, and circulation time, thereby enhancing therapeutic efficacy.

[0006] Despite these advancements in drug delivery, effective cancer treatment still relies on accurate diagnosis and monitoring. Early detection and precise therapy are critical for improving patient outcomes; however, current diagnostic methods, such as FDG-based PET imaging, often lack the necessary sensitivity and specificity for precise tumor identification and treatment evaluation. Additionally, traditional diagnostic approaches frequently involve invasive biopsy procedures and repeated radiation exposure, both of which can negatively impact the patients' quality of life. Moreover, magnetic resonance imaging (MRI) is a widely utilized diagnostic tool that provides high-resolution images; however, existing contrast agents have significant limitations, including poor specificity for cancer cells and off-target effects on healthy tissues. These agents often cause non-specific signal enhancement in healthy tissues, reducing diagnostic accuracy. Furthermore, the current targeted delivery methods have limited efficacy and may cause systemic toxicity. These limitations highlight the need for integrated strategies that combine advanced agent delivery systems with improved diagnostic techniques to enhance cancer management and treatment efficacy.

[0007] In recent years, radiotheranostics, a diagnostic and therapeutic approach that combines nuclear medicine imaging with treatment, has been increasingly applied to tumor treatment. This strategy relies on combining therapeutic agents with imaging capabilities, often with radionuclide pairs. The success of such systems depends heavily on the stability and specificity of the delivery platform, as well as on the pharmacokinetics and in vivo retention of the functional payload. Despite ongoing research, there remain significant barriers to the development of chemically defined, multifunctional carriers capable of effectively integrating both therapeutic and diagnostic components.

[0008] Moreover, existing delivery platforms often suffer from synthetic complexity, batch-to-batch variability, and poor modularity, which hinder clinical translation. Challenges in achieving controlled conjugation of targeting peptides, chelators, and therapeutic agents within a unified architecture limit the reproducibility and regulatory compliance of these systems.

[0009] Consequently, there is a continuing need in the field of targeted oncology for delivery vectors that are not only biologically effective but also synthetically tractable and clinically viable.

[0010] BRIEF DESCRIPTION OF THE INVENTION

[0011] The present invention addresses the aforementioned challenges and aims to provide a radioisotopelabeled therapeutic agent specifically designed for integrin-positive tumors.

[0012] The present invention also provides diagnostic and / or therapeutic probe, featuring the same or a similar structural framework. By incorporating an integrin-binding structure, it demonstrates significantly enhanced accumulation efficiency and prolonged retention time in integrin-positive tumors. Furthermore, the present invention further suggests favorable pharmacokinetic properties and therapeutic performance.

[0013] According to one aspect of the invention, in addition to radiolabeled applications, the compound or the conjugate in accordance with the present invention is also suitable for coordination with non-radioactive metal ions, such as gadolinium (Gd3+), allowing use as a contrast agent in magnetic resonance imaging (MRI).

[0014] The present invention provides an integrin-targeted radiotheranostics approach that supports personalized medicine by optimizing treatment while reducing the burden on patients.

[0015] The present invention also provides compounds or conjugates with identical or closely related structures labeled with radionuclides that have different properties, enabling both diagnosis and therapy. Diagnostic agents labeled with imaging radionuclides are used to detect the targeted tissue, estimate therapeutic effectiveness, evaluate possible side effects, and determine the appropriate dosage tailored to each patient. In accordance with the present invention, following this, therapeutic compounds labeled with radionuclides designed for treatment can be administered, offering high therapeutic efficacy with minimal side effects.

[0016] Another objective of the present invention is to provide a theranostic platform that enables the simultaneous delivery of diagnostic agents, and therapeutic payloads, offering both imaging and treatment functionalities. This integrated approach not only enhances treatment precision but also allows for real-time monitoring of therapeutic efficacy. In one aspect, the present invention introduces a polymer-based delivery system for the administration of anti-cancer agents. This system incorporates cleavable linkers that ensure controlled agent release within the tumor microenvironment, enhancing safety and efficacy.

[0017] It is another objective of the present invention to provide a pharmaceutical composition for the diagnosis and treatment of solid tumors.

[0018] The present invention provides a carrier platform functionalized with a chelating agent. The carrier platform has a Formula I as follows:

[0019] MBD

[0020] Formula I

[0021] According to Formula I, ITP represents an integrin-targ eting peptide that comprises cRGD, linear RGD or iRGD, MBD represents a metal-ion binding domain comprising a bifunctional chelating agent and Pu is a polymeric unit.

[0022] The polymeric unit (Pu) has a Formula II as follows:

[0023] Formula II

[0024] According to Formula II, x is a number between 15 and 300; y is a number between 1 and 100; and n is a number between 2 and 20.

[0025] The present invention provides optimization and co-development to reduce costs, making advanced therapies more accessible while lowering healthcare expenditures by focusing on effective treatments.

[0026] The present invention also provides a novel radiotheranostic platform suitable for use as diagnostic or imaging agents, for example, for use in positron emission tomography. The present invention also provides a carrier for use as diagnostic or imaging agents, for example, for use in magnetic resonance imaging. The present invention relates to a multifunctional carrier platform designed for targeted delivery to integrin-overexpressing tissues and tumors.

[0027] DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention aims to address these challenges by developing and bringing to a new theranostic agent by targeting the integrin receptors that are overexpressed on solid tumor cells. The present invention enables both diagnostic imaging and / or therapeutic intervention through the same nano-carrier using a different radioisotope for each purpose.

[0029] The present invention presents a multifunctional carrier platform for targeted delivery to integrin- overexpressing tumors.

[0030] The term “carrier platform” or the “carrier” as used herein refers to a structure for enabling multivalent attachment of targeting and functional modules.

[0031] The terms "polymeric unit" and "polymer backbone" are used interchangeably and refer to a polymer chain that includes side chains or pendant groups. For example, a side chain may include an oligoethylene glycol unit, while a pendant group may bear a therapeutic agent, a diagnostic agent, radionuclide, a targeting moiety or various linkers.

[0032] As used herein, the term ’’chelating agent” refers to a bifunctional molecule capable of forming a coordination complex with a metal ion, such as DOTA or NOTA derivatives. The carrier platform further comprises at least one bifunctional chelating agent which is covalently bound to the platform and allows coordination with metal ions. Preferred bifunctional chelating agents include DOTA, NOTA, or their derivatives. These groups may coordinate radioactive isotopes or diagnostic or therapeutic radiopharmaceutical use. These groups may also coordinate nonradioactive metal ions, such as Gd3+enabling non-radiative diagnostic imaging. The carrier platform according to one aspect of the invention, the metal-ion binding domain further comprises at least one chelating agent that is selected from the group consisting of DFO, DOTA, CB-D02A, 3p-C-DEPA, TCMC, DBCO, DIBO, BARAC, DIMAC, Oxo-DO3A, TE2A, CB-TE2A, CB- TE1A1P, CB-TE2P, MM-TE2A, DM-TE2A, diamsar, NODASA, NOD AGA, NOTA, NETA, TACN-TM, DTPA, 1B4M-DTPA, CHX-A"-DTPA, TRAP, NOPO, AAZTA, DATA, H2dedpa, H.ioctapa, F azapa, Hsdecapa, Hephospa, HBED, SHBED, BPCA, CP256, PCTA, HEHA, PEPA, EDTA, TETA, or TRITA.

[0033] The coordination of metal ions may result metal-chelate complexes exhibit high in vivo stability, minimizing metal dissociation and off-target accumulation.

[0034] The term ’’integrin-binding peptide” as used in this application includes cRGD, linear RGD, iRGD and functionally equivalent analogues thereof. The integrin-binding peptide comprises at least one peptide capable of specifically binding to integrin receptors, particularly av0v av05 and av06. The term “integrin-binding peptide” includes, but is not limited to, cyclic RGD (cRGD), linear RGD, iRGD, or analogues and derivatives thereof. These peptides may be conjugated to the polymer backbone via a linker, which may be cleavable or non-cleavable, depending on the intended pharmacokinetics. The binding affinity of these peptides facilitates receptor-mediated endocytosis or tumor vasculature accumulation, thus enhancing the targeted delivery profile.

[0035] According to the present application, the term “RGD” refers to Arg-Gly-Asp peptides comprising cyclic RGD (RGDfK) (SEQ ID NO: 1), linear RGD (SEQ ID NO: 2 to 5), or iRGD (CRGDKGPDC) (SEQ ID NO: 6).

[0036] The term “integrin-positive tumor” or “over-expressing integrin” refers to a type of growth characterized by the over-expression of integrin proteins on the surface of the tumor cells. In the context of tumors, integrins contribute significantly to the behavior and progression of cancer cells. Identifying integrin-positive tumors aid in the development of targeted therapies aimed at inhibiting integrin-mediated pathways. The polymeric carrier disclosed in the present invention facilitates active targeting by targeting moieties that specifically bind to integrin receptors found on the surface of solid tumors, such as av03 integrin, av05 integrin, and / or av06 integrin. Cellspecific binding of RGD peptides to integrin receptors that are over-expressed on the outer surface of solid tumor cells is achieved by the present invention. The process of endocytosis, which is triggered by the interaction between targeting ligands and corresponding receptors, contributes to a higher concentration inside the cells, which provides an enhanced therapeutic effect. The terms “integr in-positive tumor”, “overexpression of integrin”, “integrin-positive cancer”, and “overexpression of integrin” can be used interchangeably to describe tumors or cancers that have high levels of integrin proteins on the surface of their cells.

[0037] Over-expressed integrins in cancer according to present invention include integrin a Pv avPs, avPe and / or asPi. The percentages of integrin expression (avP3, avPs, avPe) can vary significantly between tumor samples. For example, if the expression levels of avp3, avPs, or avPe are in the range of 15-56%, the term "integrin-positive" or "over-expression of integrin" is used to define the term. For avp3, avPs, and / or avPe, when the expression levels of each, or a combination of two or all three integrins, fall within the ranges of 5-95%, 10-85%, 24-70%, or 30-60%, the term "over-expression of integrin" or "integrin-positive" can be used.

[0038] The RGD sequences (i.e. cRGD, iRGD or linear RGD) are peptides containing arginine (R), glycine (G), and aspartic acid (D). In accordance with the invention, RGD peptides are used as an integrin binding ligands that specifically bind to integrins that are often over-expressed in cancer cells and play a crucial role in tumor growth, angiogenesis, and metastasis. RGD sequence is recognized by several integrin receptors, particularly those involved in tumor progression, such as avp3, avPs, and avPe integrins. As used herein, the terms ‘RGD sequences’ and ‘RGD peptides’ are used interchangeably, and may refer to SEQ ID Nos: 1 to 6. By conjugating RGD peptides to nanomedicines, the cargo is preferentially delivered to the tumor cells. This enhances the concentration of the cargo at the tumor site while minimizing systemic toxicity.

[0039] Moreover, the over-expression of integrins also refers to the condition where these receptors are produced at levels significantly higher than what is typically observed in normal, healthy cells. In healthy cells, integrin expression levels are tightly regulated to maintain normal cellular functions such as adhesion, migration, and signal transduction. Normal expression levels are usually quantified using techniques like flow cytometry, immunohistochemistry, or Western blotting, and are presented as a baseline or control value. The overexpression of integrins can be defined by a significant increase in integrin levels compared to the baseline expression in normal cells. This can be quantified as fold changes (a common threshold being a 2-fold or greater increase) relative to normal levels. Various quantitative methods can be used for determining overexpression of the integrin such as flow cytometry, immunohistochemistry and western blotting: This method measures the protein levels of integrins in cell lysates. Overexpression is determined by comparing the band intensity corresponding to integrins in cancer cells to that in normal cells. Some studies on breast cancer cells have shown that primary breast cancer cells exhibit over-expression of integrin a p? compared to normal breast epithelial cells. This significant increase in integrin a p? expression in cancer cells as opposed to normal cells illustrates how overexpression is defined: normal cells might have 10,000 integrin molecules per cell, while cancer cells can have levels up to ten times higher, around 100,000 molecules per cell, demonstrating the contrast between normal and pathological states (https: / / doi.org / 10.1186 / 1471-2407-ll-293) (https: / / doi.org / 10.1186 / 1475-2867-7-16).

[0040] The present invention also provides compounds comprising RGD ligands that can selectively bind certain integrin receptors and a chelator capable of binding radionuclides. These compounds enable the targeted delivery of radionuclides to tumor cells, thereby providing high specificity in binding and interaction. As a result, interaction with the integrin receptors targeted by the compounds allow for selective association with the desired cell.

[0041] The invention further discloses the preparation and use of compositions that include an RGD ligand for targeting integrin receptors and a chelator for radionuclides. The compounds disclosed herein are intended to target the desired receptors in both in vitro and in vivo applications. Additionally, combining the RGD ligand with the chelator supports the safe and efficient transport of the relevant radionuclide. During use of the compound, the chelating moiety of the compound reacts with a radionuclide. When the radionuclide-peptide-polymer complex is administered to the patient intravenously, the complex binds to the integrin receptors on the tumor cells. This targeting ensures that the radiation focuses on the tumor while reducing the risk of harm to healthy tissues. The bound radionuclide emits ionizing radiation over a short distance, causing DNA damage.

[0042] In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of solid tumors. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of breast cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of an ovarian cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a lung cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a liver cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a head and neck cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a prostate cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a colon adenocarcinoma. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a pancreatic cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the diagnosis of a brain cancer.

[0043] In a possible embodiment, the present invention discloses a a labeled carrier platform having Formula I for use in the treatment of solid tumors. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a breast cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of an ovarian cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of lung cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a liver cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a head and neck cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a prostate cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of the colon adenocarcinoma. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a pancreatic cancer. In a possible embodiment, the present invention discloses a labeled carrier platform having Formula I for use in the therapy or treatment of a brain cancer.

[0044] In one embodiment of the invention, the carrier platform further comprises a first linker, Li, that connects the metal-ion binding domain to the polymer unit (Pu). The first linker (Li) comprises functional groups that are amide, carbamate or thiourea. In a further embodiment the polymeric unit is of Formula III:

[0045] Formula III According to this embodiment, x is a number between 15 and 300; y is a number between 2 and 100; and n is a number between 2 and 20.

[0046] In accordance with yet another embodiment, the first linker (Li) is selected from the group consisting of:

[0047] In accordance with another possible embodiment, the polymeric unit comprises two or more PEG units having the Formula IV:

[0048] Formula IV

[0049] According to the Formula IV, x is a number between 15 and 300; y is a number between 2 and 100; n is a number between 2 and 20; and m is a number between 2 and 20. In yet another embodiment, the carrier platform has the Formula V:

[0050]

[0051] Formula V

[0052] According to Formula V, n is a number between 2 and 20; x is a number between 15 and 300; y is a number between 2 and 100; and m is a number between 2 and 20. According to yet another embodiment, the carrier platform has the Formula VI:

[0053]

[0054] Formula VI

[0055] According to the Formula VI, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In accordance with another embodiment, the carrier platform has the Formula VH:

[0056]

[0057] Formula VII

[0058] According to Formula VII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In an alternative embodiment, the carrier platform has the Formula VIII:

[0059]

[0060] According to Formula VIII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another alternative embodiment, the carrier platform has the Formula IX: According to Formula IX, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100.

[0061] In one embodiment of the invention, the carrier platform has the Formula X:

[0062] Formula X

[0063] According to Formula X, n is a number between 2 and 20; x is a number between 15 and 300; y is a number between 2 and 100; and m is a number between 2 and 20.

[0064] In another embodiment of the invention, the carrier platform has the Formula XI:

[0065]

[0066] Formula XI

[0067] According to Formula XI, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XII:

[0068]

[0069] Formula XII

[0070] According to Formula XII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XIII:

[0071]

[0072] According to Formula XIII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XIV: According to Formula XIV, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100.

[0073] In another embodiment of the invention, the carrier platform has the Formula XV:

[0074] Formula XV

[0075] According to Formula XV, n is a number between 2 and 20; x is a number between 15 and 300; y is a number between 2 and 100; and m is a number between 2 and 20.

[0076] In another embodiment of the invention, the carrier platform has the Formula XVI:

[0077] Formula XVI

[0078] According to Formula XVI, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XVII:

[0079]

[0080] Formula XVII

[0081] According to Formula XVII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XVIII:

[0082]

[0083] According to Formula XVIII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XIX:

[0084]

[0085] Formula XIX

[0086] According to Formula XIX, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XX, According to Formula XX, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100.

[0087] In another embodiment of the invention, the carrier platform has the Formula XXI,

[0088] Formula XXI

[0089] According to Formula XXI, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100.

[0090] In another embodiment of the invention, the carrier platform has the Formula XXII:

[0091]

[0092] Formula XXII

[0093] According to Formula XXII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XXIII:

[0094]

[0095] Formula XXIII

[0096] According to Formula XXIII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XXIV:

[0097]

[0098] Formula XXIV

[0099] According to Formula XXIV, n is a number between 2 and 20; x is a number between 15 and 300, y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XXV,

[0100]

[0101] Formula XXV

[0102] According to Formula XXV, n is a number between 2 and 20; x is a number between 15 and 300, y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XXVI,

[0103]

[0104] Formula XXVI

[0105] According to Formula XXVI, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100. In another embodiment of the invention, the carrier platform has the Formula XXVII, According to Formula XXVII, n is a number between 2 and 20; x is a number between 15 and 300; and y is a number between 2 and 100.

[0106] In another embodiment of the invention, the carrier platform has the Formula XXVIII:

[0107] Formula XXVIII

[0108] According to Formula XXVIII, n is a number between 2 and 20; x is a number between 15 and

[0109] 300; and y is a number between 2 and 100.

[0110] In possible embodiments; x is a number between 15 and 300, y is a number between 20 and 100, x is a number between 30 and 200 or x is a number between 45 and 150 or x is a number between 60 and 100.

[0111] In possible embodiments; y is a number between 1 and 100; or y is a number between 2 and 80; y is a number between 5 and 60 or y is a number between 15 and 50 or y is a number between 20 and 40.

[0112] In possible embodiments; n is a number between 1 and 20 or n is 3 or n is 4 or n is a number between 5 and 15 or n is a number between 6 and 10. Herein, n can be either an integer or a decimal number like 3.5. In a further aspect, the present invention provides a theranostic kit comprising: a) a carrier platform or a complex according to Formula I to Formula XXVIII, b) at least one radionuclide-including compound configured for imaging cancer cells or monitoring cancer progression.

[0113] In a particular embodiment of the present disclosure, the present invention provides a theranostic kit comprising at least one radionuclide-including labeled carrier platform configured for the targeted treatment of cancer cells.

[0114] A possible embodiment of the present invention is arranged as a complex of the chelating agent with metal ions, and as conjugates of these complexes with a biological carrier. According to another possible embodiment, the present invention relates to chelates for radiometals useful in molecular imaging and therapy, in particular, to radioisotopes of gallium (Ga) such as Ga-66, Ga- 67, and Ga-68 or to radioisotopes of zirconium (Zr) such as Zr-89 or to radioisotopes of Lutetium (Lu) such as Lu- 177 or to radioisotopes of Actinium (Ac) such as Ac- 225 or to radioisotopes of Yttrium (Y) such as Y-90 or to radioisotopes of Copper such as Cu-64, Cu-67 or to a stable or active form of a Gadolinium metal such as Gd-157.

[0115] The present invention presents a complex comprising the carrier platform or a pharmaceutically acceptable salt thereof, and an ion of a stable form of a metal selected from a group consisting of Ga, Lu, Cu, Ac, Y or Zr.

[0116] The present invention further presents a complex comprising the carrier platform or a pharmaceutically acceptable salt thereof, and an ion of a radionuclide selected from a group consisting of Ga, Lu, Cu, Ac, Y or Zr.

[0117] In accordance with an aspect of the invention, a complex comprises the carrier platform or a pharmaceutically acceptable salt thereof, and an ion of Gd.

[0118] In accordance with an aspect of the invention, a carrier platform further comprises at least one metal selected from the group consisting of Zr-89, Ac-225, Y-90, Lu-177, Ga-68, Cu-64, Cu-67, Gd-157. A preferred embodiment of the present invention is a radioisotope-labeled carrier platform that is used as a therapeutic agent represented by the above-mentioned chemical Formula I to Formula XXVIII.

[0119] According to the radioisotope-labeled carrier platform of the present invention, the radioisotopelabeled diagnostic agent and / or the radioisotope-labeled therapeutic agent include an integrin- binding ligand. This ligand specifically targets integrin receptors that are over-expressed in solid tumors, enabling the carrier platform to selectively bind to these receptors. Upon administration, the carrier platform circulates through the bloodstream and preferentially accumulates at the primary tumor site or metastatic lesions in organs. This targeting mechanism facilitates precise imaging and effective treatment, supporting both diagnostic and therapeutic applications in integrin-positive solid tumors.

[0120] This radioisotope-labeled carrier platform is preferably designed as a theranostic agent, combining the diagnostic and therapeutic capabilities of the radioisotope-labeled agents, providing targeted imaging and treatment for integrin-positive tumors.

[0121] A radioisotope- labeled diagnostic agent can be formed by combining, within the scope of Formula I, a diagnostic carrier platform containing radionulides (Zr-89, Ga-68, or Cu-64) and a therapeutic carrier platform containing radionulides (Lu- 177, Ac-225, Y-90 or Cu-67). In exemplary embodiment, specific theranostic pairs include Zr-89 (diagnostic) / Lu- 177 (therapeutic), or Ga- 68 (diagnostic) / Lu-177 (therapeutic), or Cu-64 (diagnostic) / Cu-67 (therapeutic).

[0122] In one embodiment, a carrier platform comprises a radionuclide which enables the imaging of cancer cells, wherein said radionuclide is Ga-68. In another embodiment, a carrier platform comprises a radionuclide which enables imaging of cancer cells, wherein said radionuclide is Zr- 89. In a possible embodiment, a carrier platform comprises a radionuclide which enables imaging of cancer cells, wherein said radionuclide is Cu-64. In another possible embodiment, a carrier comprises a metal ion which enables imaging of cancer cells, wherein said ion is Gd-157.

[0123] According to another aspect of the invention, a carrier platform comprises a radionuclide which enables the destruction of cancer cells, wherein said radionuclide is Lu- 177. In another embodiment, a carrier platform comprises a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Ac-225. In another possible embodiment, a carrier platform comprises a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Y-90. In a possible embodiment, a carrier platform comprises a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Cu-67.

[0124] In accordance with the invention, these radioisotope-labeled diagnostic agents are utilized as a radiotheranostic agent, where the radioisotope-labeled integrin-binding structure-labeled diagnostic agent and the radioisotope-labeled therapeutic agent share the same skeleton or a skeleton equipped with an MBD suitable for the radionuclide. Both agents are absorbed, distributed, metabolized, and excreted in approximately the same manner. This allows the diagnostic agent to be administered in advance to evaluate predicted effectiveness, dosage, administration method, organ specificity, and accumulation at the primary tumor or metastatic lesions. Based on this diagnostic assessment, an appropriate dose of the radioisotope-labeled therapeutic agent is then administered to deliver targeted radiation therapy. Moreover, the present invention demonstrates significantly superior accumulation efficiency and retention time in primary tumor or metastatic lesions. This makes it exceptionally effective for radioisotope-based imaging and therapeutic applications targeting integrin-positive primary tumors or metastases.

[0125] The invention incorporates a peptide that specifically targets integrin receptors, while the polymer is equipped with a chelator to accommodate a variety of radionuclides. Among these radionuclides, gallium-68 (68Ga) and zirconium-89 (89Zr) are notably suited for PET imaging, whereas lutetium- 177 (177Lu) provides a therapeutic effect. This combination constitutes a theranostic pair, enabling highly specific targeting of tumor tissue.

[0126] By using68Ga or89Zr for imaging, clinicians can promptly determine whether a patient’s tumor overexpresses integrin receptors and can swiftly proceed to therapy with177Lu. For diagnostic purposes, integrin receptor targeting is being extended to create a novel PET imaging platform with68Ga and89Zr as the radionuclides.

[0127] Receptor-mediated targeting of tumor tissue offers (i) high-resolution imaging, (ii) insights into whether the same targeting approach will be efficacious for treatment, and (iii) a means of evaluating treatment effectiveness. Compared with traditional18F-FDG PET imaging, present invention delivers superior specificity and sensitivity.

[0128] Coupling the polymer of the invention with68Ga enables clinicians to monitor the effects of integrin-targeted agents, essentially in serving as a diagnostic companion to such therapies. Meanwhile, the integrin-targeted carrier platform of the present invention conjugated with177Lu represents a powerful new therapeutic option.

[0129] In accordance with the present invention, the carrier platform including DOTA (1,4,7,10- tetraazacyclododecane-l,4,7,10-tetraacetic acid) can form chelate complexes with trivalent metals that exhibit high stability. This ensures efficient transport and stability of the radioisotope to the target region, while minimizing the spread of radiation to surrounding tissues. Furthermore, the polymer disclosed in this invention enhances the biological properties of targeting agents. By forming a trivalent metal complex, the binding of DOTA to the polymer can prolong the agent’s circulation time, improve tumor-targeting capacity, and increase therapeutic efficacy.

[0130] In accordance with the present invention, the carrier platform including NOTA (1,4,7- triazacyclononane-l,4,7-triacetic acid) can form highly stable chelate complexes with trivalent metals, especially with gallium (Ga-68). This ensures efficient transport and stability of the radioisotope to the target region, while minimizing spread of radiation to surrounding tissues. By forming a stable complex with NOTA, the binding to the polymer can extend the agent’s circulation time, improve its ability to target tumors, and enhance therapeutic efficacy.

[0131] In accordance with the present invention, the carrier platform including TETA is capable of forming stable chelate complexes with divalent and trivalent metals, for example copper isotopes (Cu-64 and Cu-67). These stable complexes facilitate the precise transport of the radioisotope to the tumor site and reduce off-target radiation exposure. The incorporation of TETA into the polymer disclosed increases circulation time, optimizes tumor targeting, and enhances the therapeutic and diagnostic performance of the agent.

[0132] In accordance with the present invention, the carrier platform including DiAmSar (1,8-diamino- 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane) can form highly stable chelate complexes, particularly with copper isotopes (Cu-64 and Cu-67) and other metals with high affinity for this chelator. These complexes exhibit exceptional kinetic and thermodynamic stability, ensuring accurate delivery of the radioisotope to the target site while minimizing radiation exposure to nontarget tissues.

[0133] In accordance with the present invention, the carrier platform including Cb-TE2A (1,4,8,11- tetraazabicyclo[6.6.2]hexadecane-4, 11 -diacetic acid) is highly effective in forming stable chelate complexes with copper isotopes (Cu-64 and Cu-67) due to its rigid, pre-organized structure. This ensures robust radioisotope binding and minimizes the risk of dissociation during transport, leading to efficient delivery of the isotope to the tumor site.

[0134] In accordance with the invention, the RGD- and chelator-including polymeric carrier platform is capable of forming complexes with radionuclides selected from the group consisting of64Cu,124I,86Y,89Zr,68Ga,18F,nC,125I,1241,131I,1231,1311,1231,32C1,33C1,34C1,68Ga,74Br,75Br,76Br,77Br,78Br,89Zr,186Re,188Re,90Y,177Lu, "Tc, or153Sm, thereby enabling the polymeric carrier platform to form stable complexes for diagnostic or therapeutic applications.

[0135] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Zr-89.

[0136] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Ga-68.

[0137] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Lu-177.

[0138] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Cu-64.

[0139] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Cu-67.

[0140] In another exemplary embodiment, RGD- and chelator- containing polymeric carrier platform is capable of being labeled with Gd-157. In an optional embodiment, the radioisotope-labeled carrier platform comprises RGD (i.e., cyclic RGD, linear RGD, or iRGD) as an integrin-binding ligand. In accordance with the invention, the carrier platform comprising RGD can be radiolabeled with Zr-89 using a covalently bound chelator. In one exemplary embodiment, the covalently bound chelator is DOTA (1,4,7,10- tetraazacyclododecane-l,4,7,10-tetraacetic acid). In another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Zr-89 using NOTA (1,4, 7-triazacyclononane- 1,4,7-triacetic acid) as a covalently bound chelator. In another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Zr-89 using DTPA (diethylenetriaminepentaacetic acid) as a covalently bound chelator. In another exemplary embodiment, the polymeric carrier platform comprising RGD can be radiolabeled with Zr-89 using TETA(l,4,8,ll-tetraazacyclotetradecane-l,4,8,ll-tetraacetic acid) as a covalently bound chelator. In another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Zr-89 using CB-TE2A as a covalently bound chelator. In yet another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Zr-89 using DiAmSar as a covalently bound chelator.

[0141] In an optional embodiment, the radioisotope-labeled carrier platform comprises RGD (i.e., cyclic RGD, linear RGD, or iRGD) as an integrin-binding ligand. In accordance with the invention, the carrier platform comprising RGD can be radiolabeled with Lu- 177 using a covalently bound chelator; in one exemplary embodiment, the covalently bound chelator is DOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Lu- 177 using NOTA; in another exemplary embodiment, the polymeric carrier platform comprising RGD can be radiolabeled with Lu- 177 using DTPA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Lu- 177 using TETA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Lu- 177 using CB- TE2A; and in yet another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Lu- 177 using DiAmSar.

[0142] In an optional embodiment, the radioisotope-labeled carrier platform comprises RGD (i.e., cyclic RGD, linear RGD, or iRGD) as an integrin-binding ligand. In accordance with the invention, the carrier platform comprising RGD can be radiolabeled with Ga-68 using a covalently bound chelator; in one exemplary embodiment, the covalently bound chelator is DOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Ga-68 using NOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Ga-68 using DTPA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Ga-68 using TETA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Ga-68 using CB-TE2A; and in yet another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Ga-68 using DiAmSar.

[0143] In an optional embodiment, the radioisotope-labeled carrier platform comprises RGD (i.e., cyclic RGD, linear RGD, or iRGD) as an integrin-binding ligand. In accordance with the invention, the carrier platform comprising RGD can be radiolabeled with Cu-64 using a covalently bound chelator; in one exemplary embodiment, the covalently bound chelator is DOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-64 using NOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-64 using DTPA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-64 using TETA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-64 using CB-TE2A; and in yet another exemplary embodiment, carrier platform comprising RGD can be radiolabeled with Cu- 64 using DiAmSar.

[0144] In an optional embodiment, the radioisotope-labeled carrier platform comprises RGD (i.e., cyclic RGD, linear RGD, or iRGD) as an integrin-binding ligand. In accordance with the invention, the carrier platform comprising RGD can be radiolabeled with Cu-67 using a covalently bound chelator; in one exemplary embodiment, the covalently bound chelator is DOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-67 using NOTA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-67 using DTPA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-67 using TETA; in another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-67 using CB-TE2A; and in yet another exemplary embodiment, the carrier platform comprising RGD can be radiolabeled with Cu-67 using DiAmSar. The present invention further comprises at least one end group. The term "end group" can be represented by E. The end group refers to functionalities or constitutional units that are at the extremity of a polymer. E is optionally a polymerization initiator or a fragment thereof. Particularly when an initiator is used in the polymerization reaction, the initiator fragment may stay as an end group to the polymer. The initiator used herein may be any material suitable for initiating the polymerization reaction known in the art. E may further be represented by A or B. A is an end group that is a polymerization initiator, a chain transfer agent or a fragment thereof; B is an end group that is a polymerization initiator, a chain transfer agent or a fragment thereof. When an initiator is used in the polymerization reaction, it may remain as an end group to the polymer. The initiator used herein may be any material suitable for initiating the polymerization reaction known in the art. The patent application WO2018002761 Al also describes the end groups, and this document is incorporated herein by reference. In a possible embodiment, the carrier platform may comprise one or more end group that is a polymerization initiator or chain transfer agent that is a part of a trithiocarbonate or a dithioate. In another possible embodiment, the end group may be selected from the group consisting of 3,5-Bis(2-dodecylthiocarbonothioylthio-l- oxopropoxy)benzoic acid, 3-Butenyl 2-(dodecylthiocarbonothioylthio)-2-methylpropionate, 4- Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid, 4-Cyano-4-

[0145] [(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol, Cyanomethyl dodecyl, Cyanomethyl [3- (trimethoxysilyl)propyl] trithiocarbonate, 2-Cyano-2-propyl dodecyl trithiocarbonate, S,S- Dibenzyl trithiocarbonate, 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 2-(Dodecylthiocarbonothioylthio)-2- methylpropionic acid N-hydroxysuccinimide ester, 2-(Dodecylthiocarbonothioylthio)-2- methylpropionic acid pentafluorophenyl ester, 2-(Dodecylthiocarbonothioylthio)propionic acid, Methyl 2-(dodecylthiocarbonothioylthio)-2-methylpropionate, Pentaerythritol tetrakis[2- (dodecylthiocarbonothioylthio)-2-methylpropionate], Phthalimidomethyl butyl trithiocarbonate, 1,1,1 -Tris[(dodecylthiocarbonothioylthio)-2-methylpropionate] ethane, benzyl benzodithioate, Cyanomethyl benzodithioate, 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid, 4-Cyano-4- (phenylcarbonothioylthio)pentanoic acid N-succinimidyl ester, 2-Cyano-2-propyl benzodithioate, 2-Cyano-2-propyl 4-cyanobenzodithioate, Ethyl 2-(4-methoxyphenylcarbonothioylthio)acetate, Ethyl 2-methyl-2-(phenylthiocarbonylthio)propionate, Ethyl 2-(phenylcarbonothioylthio)-2- phenylacetate, Ethyl 2-(phenylcarbonothioylthio)propionate, 1 -(Methoxy carbonyl)ethyl benzodithioate, 2-(4-Methoxyphenylcarbonothioylthio)ethanoic acid, 4-cyano-4- (phenylcarbonothioylthio)pentanoate, 2-(Phenylcarbonothioylthio)propanoic acid, 2-Phenyl-2- propyl benzodithioate, Cyanomethyl methyl(4-pyridyl)carbamodithioate, Cyanopropan-2-yl N- methyl-N-(pyridin-4-yl)carbamodithioate, Methyl 2-[methyl(4- pyridinyl)carbamothioylthio]propionate or 1 -Succinimidyl-4-cyano-4-[N-methyl-N-(4- pyridyl)carbamothioylthio]pentanoate.

[0146] In accordance with another embodiment of the invention, a PEG-based carrier platform comprises the polymeric unit, the second linker and radionuclide binding domain, and have the Formula

[0147] XXIX:

[0148] Formula XXIX

[0149] In accordance with another embodiment of the invention, a PEG-based carrier platform comprises the polymeric unit, the second linker and radionuclide binding domain, and have the Formula XXX:

[0150]

[0151] Formula XXX

[0152] In another embodiment E is a fragment of a polymerization initiator and they have the same chemical structure. In one embodiment, E is selected from the group consisting of 4,4'-Azobis(4- cyanovaleric acid), 4,4'-Azobis(4-cyanovaleric acid), l,l'-Azobis(cyclohexanecarbonitrile), 2,2'- Azobis(2-methylpropionamidine) dihydrochloride, 2,2'-Azobis(2-methylpropionitrile) (also known as AIBN), Ammonium persulfate, hydroxymethanesulfinic acid monosodium salt dihydrate, potassium persulfate, sodium persulfate, tert-Butyl hydroperoxide, tert-Butyl peracetate, Cumenehydroperoxide, 2,5-Di(tert-butylperoxy)-2,5-dimethyl-3-hexyne, Dicumyl peroxide, 2,5-Bis(tert-butylperoxy)-2,5-dimethylhexane, l,l-Bis(tert-butylperoxy)-3,3,5- trimethylcyclohexane, l,l-Bis(tert-amylperoxy)cyclohexane, Benzoyl peroxide, 2-Butanone peroxide, tert-Butyl peroxide, Di-tert-amyl peroxide, Lauroyl peroxide, tert-Butyl peroxybenzoate, tert-Butylperoxy 2-ethylhexyl carbonate, tert-Butyl hydroperoxide, 2- Azidoethyl 2-bromoisobutyrate, Bis[2-(2-bromoisobutyryloxy)undecyl] disulfide, Bis[2-(2'- bromoisobutyryloxy)ethyl]disulfide, 2-Bromoisobutanoic acid N-hydroxysuccinimide ester, 2- Bromoisobutyric anhydride, a-Bromoisobutyryl bromide, 2-(2-Bromoisobutyryloxy)ethyl methacrylate, tert-Butyl a-bromoisobutyrate, 3-Butynyl 2-bromoisobutyrate, Dipentaerythritolhexakis(2-bromoisobutyrate), Dodecyl 2-bromoisobutyrate, Ethyl a- bromoisobutyrate, Ethylene bis(2-bromoisobutyrate), 2-Hydroxy ethyl 2-bromoisobutyrate, 1- (DL-1,2-Isopropylideneglyceryl) 2-bromoisobutyrate, Methyl a-bromoisobutyrate, Octadecyl 2- bromoisobutyrate, Pentaerythritoltetrakis(2-bromoisobutyrate), 1 -(Phthalimidomethyl) 2- bromoisobutyrate, Poly(ethylene glycol) bis(2-bromoisobutyrate), Propargyl 2-bromoisobutyrate, l,l,l-Tris(2-bromoisobutyryloxymethyl)ethane, 10-Undecenyl 2-bromoisobutyrate, N-tert-Butyl- O-[l-[4-(chloromethyl)phenyl]ethyl]-N-(2-methyl-l-phenylpropyl)hydroxylamine, N-tert-Butyl- N-(2-methyl-l-phenylpropyl)-O-(l-phenylethyl)hydroxylamine, TEMPO, TEMPO methacrylate, 2,2,5-Trimethyl-4-phenyl-3-azahexane-3-nitroxide, 3,5-Bis(2-dodecylthiocarbonothioylthio-l - oxopropoxy )benzoic acid, 3-Butenyl 2-(dodecylthiocarbonothioylthio)-2-methylpropionate, 4- Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid, 4-Cyano-4-

[0153] [(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol, Cyanomethyl dodecyl, Cyanomethyl [3- (trimethoxysilyl)propyl] trithiocarbonate, 2-Cyano-2-propyl dodecyl trithiocarbonate, S,S- Dibenzyl trithiocarbonate, 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 3 -azido- 1 -propanol ester, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid N-hydroxysuccinimide ester, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid pentafluorophenyl ester, 2- (Dodecylthiocarbonothioylthio)propionic acid, Methyl 2-(dodecylthiocarbonothioylthio)-2- methylpropionate, Pentaerythritol tetrakis[2-(dodecylthiocarbonothioylthio)-2- methylpropionate], Phthalimidomethyl butyl trithiocarbonate, 1,1,1-

[0154] Tris[(dodecylthiocarbonothioylthio)-2-methylpropionate]ethane, benzyl benzodithioate, Cyanomethyl benzodithioate, 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid, 4-Cyano-4- (phenylcarbonothioylthio)pentanoic acid N-succinimidyl ester, 2-Cyano-2-propyl benzodithioate, 2-Cyano-2-propyl 4-cyanobenzodithioate, Ethyl 2-(4-methoxyphenylcarbonothioylthio)acetate, Ethyl 2-methyl-2-(phenylthiocarbonylthio)propionate, Ethyl 2-(phenylcarbonothioylthio)-2- phenylacetate, Ethyl 2-(phenylcarbonothioylthio)propionate, 1 -(Methoxy carbonyl)ethyl benzodithioate, 2-(4-Methoxyphenylcarbonothioylthio)ethanoic acid, 2-Nitro-5-(2- propynyloxy)benzyl, 4-cyano-4-(phenylcarbonothioylthio)pentanoate, 2-

[0155] (Phenylcarbonothioylthio)propanoic acid, 2-Phenyl-2-propyl benzodithioate, Cyanomethyl methyl(4-pyridyl)carbamodithioate, Cyanopropan-2-yl N-methyl-N-(pyridin-4- yl)carbamodithioate, Methyl 2-[methyl(4-pyridinyl)carbamothioylthio]propionate, 1- Succinimidyl-4-cyano-4-[N-methyl-N-(4-pyridyl)carbamothioylthio]pentanoate or any fragment of the initiators listed herein. The linker can also be a C1-C10 hydrocarbon or a C1-C10 substituted or hetero substituted hydrocarbon such that it comprises a functional group that dissociates under physiological conditions, such as an acetal, ester, imine, amide, disulfide, carbonate, carbamate, hydrazone. The term "C1-C10 hydrocarbon" refers to a hydrocarbon chain having 1 to 10 C atoms in the backbone. The term "C1-C10 substituted hydrocarbon" refers to a hydrocarbon chain having 1 to 10 C atoms in the backbone wherein one or more of its hydrogen atoms replaced by atoms of groups of other elements such as alcohol, amine, carboxyl or thiol.

[0156] The term "Ci-Cio heterosubstituted hydrocarbon" refers to a hydrocarbon chain having 1 to 10 C atoms in the backbone wherein at least one of the C atoms is substituted with an atom other than C such as nitrogen, oxygen, phosphorus, sulfur or a halogen atom. These substituents include but not limited to lower alkoxy such as methoxy, ethoxy, butoxy; ethers; acetals; ketals; esters; heteroaryl; heterocyclic; hydroxyl; protected hydroxyl; acyl; acyloxy; amino; amido; imine, disulfide, carbonate, carbamate, hydrazone.

[0157] In an embodiment of the invention, the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one disulfide functional group. In an embodiment of the invention the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one acetal functional group. In an embodiment of the invention the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one ester functional group. In an embodiment of the invention the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one imine functional group. In an embodiment of the invention the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one amide functional group. In an embodiment of the invention the linker is a Ci-Cio hetero substituted hydrocarbon comprising at least one carbonate functional group.

[0158] In another embodiment of the invention the linker may comprise a Ci-Cio substituted or hetero substituted hydrocarbon comprising two or more functional groups selected from the group comprising acetal, ester, imine, amide, disulfide, carbonate, carbamate, hydrazone. In another embodiment of the invention the linker may be a combination of a Ci-Cio substituted hydrocarbon comprising at least one functional group selected from the group comprising acetal, ester, imine, amide, disulfide, carbonate, carbamate, hydrazone and a peptide chain selected from the group comprising GFLG (SEQ ID NO: 7), Val-Cit or Phe-Lys or Vai- Ala or Ala-Leu- Ala-Leu (SEQ ID NO: 8).

[0159] In some of the preferred embodiments, the polymer-agent conjugate of invention comprises one or more of the following examples. Examples of the present invention will be described in detail below, but the scope of the present invention is not limited to these examples.

[0160] Examples employing the NHS-activated carbonate copolymer (Formula XXIX) are presented below.

[0161] Example 1: NHS-activated carbonate copolymer contains 4.6 repeat units (y) and 51.3 peptide repeat units; Mn = 16 657 g mol-1. The polymer was then conjugated with DOTA as the chelator.

[0162] Example 2: NHS-activated carbonate copolymer contains 4.6 repeat units (y) and 51.3 peptide repeat units; Mn = 16 700 g mol-1. The polymer was then conjugated with NOTA as the chelator. Example 3: NHS-activated carbonate copolymer contains 11.6 repeat units (y) and 51.3 peptide repeat units; Mn = 18 500 g mol-1. The polymer was then conjugated with DOTA as the chelator.

[0163] Example 4: NHS-activated carbonate copolymer contains 11.6 repeat units (y) and 51.3 peptide repeat units; Mn = 18 500 g mol-1. The polymer was then conjugated with NOTA as the chelator. Example 5: NHS-activated carbonate copolymer contains 6.8 repeat units (y) and 65.4 peptide repeat units; Mn = 21 500 g mob1. The polymer was then conjugated with DOTA as the chelator.

[0164] Example 6: NHS-activated carbonate copolymer contains 6.8 repeat units (y) and 65.4 peptide repeat units; Mn = 21 500 g mol-1. The polymer was then conjugated with NOTA as the chelator. Example 7: NHS-activated carbonate copolymer contains 11.0 repeat units (y) and 44.4 peptide repeat units; Mn = 16 300 g mol-1. The polymer was then conjugated with DOTA as the chelator.

[0165] Example 8: NHS-activated carbonate copolymer contains 11.0 repeat units (y) and 44.4 peptide repeat units; Mn = 16 300 g mol-1. The polymer was then conjugated with NOTA as the chelator.

[0166] Example 9: NHS-activated carbonate copolymer contains 2.0 repeat units (y) and 25.0 peptide repeat units; Mn = 8 100 g mob1. The polymer was then conjugated with DOTA as the chelator.

[0167] Example 10: NHS-activated carbonate copolymer contains 2.0 repeat units (y) and 25.0 peptide repeat units; Mn = 8 100 g mob1. The polymer was then conjugated with NOTA as the chelator.

[0168] Example 11: NHS-activated carbonate copolymer contains 27.6 repeat units (y) and 31.7 peptide repeat units; Mn = 17 000 g mob1. The polymer was then conjugated with DOTA as the chelator. Example 12: NHS-activated carbonate copolymer contains 27.6 repeat units (y) and 31.7 peptide repeat units; Mn = 17 000 g mob1. The polymer was then conjugated with NOTA as the chelator.

[0169] Examples employing the carbamate-linked copolymer prepared with DOTA-PEG-NH2 (Formula XXX) are presented below.

[0170]

[0171] Formula XXX

[0172] Example 13: An N-hydroxysuccinimide-activated carbamate copolymer was obtained that averages 4.6 repeat units (y) and 51.3 peptide-bearing repeat units (x) per chain, with a number- average molecular weight (Mn) of 19000 g mol-1. The strategically positioned carbamate linkages provide the key reactive handle for subsequent conjugation of 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA), thereby installing the chelating functionality.

[0173] Example 14: A second NHS-activated carbamate copolymer contains 11.6 carbamate repeat units (y) while maintaining 51.3 peptide repeat units (x); Mn= 25 200 g mol-1. As in Example 13, the reactive carbamate groups enable efficient attachment of DOTA under identical coupling conditions, yielding a higher-loading DOTA-functionalized construct. The following results describe the Gd(III)- chelated versions of the NHS-activated carbamate copolymers as shown in Formula XXXI, and firstly introduced as Example 13 and Example 14.

[0174] Formula XXXI

[0175] The copolymer including 4.6 carbamate repeat units (y) and 51.3 peptide repeat units (x) per chain (Mn = 19300 g mol1) was complexed with Gd(III) via its DOTA chelators. It was showed that 8.1 mg of this material carries 0.104 mg of Gd(III). Accordingly, a 1 mg mL1solution of polymer A supplies 0.0128 mg mL1of Gd(III), which corresponds to 8.13 x 105mM metal concentration. Increasing the carbamate content to 11.6 repeat units (while maintaining 51.3 peptide units) and scaling the chain length to Mn = 25 200 g mol1yielded polymer B. After DOTA-mediated complexation, 8.1 mg of polymer B incorporates 0.19 mg of Gd(III). On a solution basis, 1 mg mL1of polymer B delivers 0.0234 mg mL1of Gd(III), equivalent to 1.49 x 104mM.

[0176] These data underscore the direct relationship between carbamate density and metal loading that doubling the reactive carbamate sites nearly doubles the Gd(III) payload that each polymer chain can carry.

[0177] Example 15: As another exemplary embodiment, a copolymer (Formula XXXII) was synthesized with average repeat numbers x and y that bear an aryl dithiobenzoate residue at one chain end. Average repeat numbers herein and hereinbelow can be for example x = 4-6 and y = 48-51. A single carbamate linkage along the backbone was used to tether a 4-aminobutyl-DOTA moiety, while the opposite chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0178] Formula XXXII

[0179] Example 16: As yet another exemplary embodiment, a copolymer (Formula XXXIII) was synthesized with average repeat numbers x and y and bears an aryl dithiobenzoate residue at one chain end. A single carbamate linkage along the backbone was used to tether a / ?-aminobenzyl- DOTA (p-NEE-Bn-DOTA) moiety, while the opposite chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0180] Example 17: As a further exemplary embodiment, a copolymer (Formula XXXIV) was synthesized with average repeat numbers x = 45 and y = 4.5 (Mn= 14600 g mol1). It bears an aryl dithiobenzoate residue at one chain end. A single thiourea linkage along the backbone tethers a DOTA-isothiocyanate (DOTA-SCN) moiety.

[0181]

[0182] Example 18: As a further exemplary embodiment, a copolymer (Formula XXXV) was synthesized with average repeat numbers x and y. It bears an aryl dithiobenzoate residue at one chain end. A single amide linkage formed by coupling a DOTA-N-hydroxysuccinimide ester (DOTA-NHS) with a pendant amine along the backbone — tethers the DOTA moiety, while the opposite chain end is functionalized with a cyclic RGD (cRGD) peptide.

[0183] Formula XXXV Example 19: As a further exemplary embodiment, a copolymer (Formula XXXVI) was synthesized with average repeat numbers x and y. It bears an aryl dithiobenzoate residue at one chain end. A single carbamate linkage along the backbone was used to tether a DOTA-PEG-NH2 moiety, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0184] Formula XXXVI

[0185] Example 20: As a further exemplary embodiment, a copolymer (Formula XXXVII) was synthesized with average repeat numbers x (ethylene-glycol units) and y (carbonate units). It bears an aryl dithiobenzoate residue at one chain end. A single carbamate linkage along the backbone was used to tether a 4-aminobutyl-DOTA moiety, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0186]

[0187] Formula XXXVII Example 21: As a further exemplary embodiment, a copolymer (Formula XXXVIII) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone was used to tether a / ?-aminobenzyl-DOTA moiety, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide. It comprises the DOTA macrocycle, a benzyl ring appended to one of its side chains, and a free amino group located at the para position on that ring. The free NEE group enables facile conjugation to peptides, polymer backbones, or surfaces through amide, urea, or carbamate linkages, while the benzyl spacer (-QL-CsHs-) attached to one of the macrocycle nitrogens acts as a “spacer”, conferring chemical stability and synthetic convenience to the aromatic ring. The DOTA moiety simultaneously chelates metal ions with high affinity, making the molecule a widely used bifunctional chelator.

[0188] Example 22: As a further exemplary embodiment, a copolymer (Formula XXXIX) was synthesized with average repeat numbers x and y. A single thiourea linkage along the backbone formed by reaction of a pendant primary amine with / ?-isothiocyanatobenzyl-DOTA (DOTA-SCN) was used to tether the DOTA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0189]

[0190] Formula XXXIX

[0191] Example 23: As a further exemplary embodiment, a copolymer (Formula XL) was synthesized with average repeat numbers x and y. A single amide linkage along the backbone formed by coupling a pendant primary amine with DOTA-NHS ester was used to tether the DOTA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide. Example 24: As a further exemplary embodiment, a copolymer (Formula XLI) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone, formed by coupling a pendant carbonate-activated site with NOTA-PEG-NEE, was used to tether the NOTA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0192] Formula XLI

[0193] Example 25: As a further exemplary embodiment, a copolymer (Formula XLII) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with NFE-MPA A-NOD A was used to tether the NODA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0194] Formula XLII

[0195] Example 26: As a further exemplary embodiment, a copolymer (Formula XLIII) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with NEE-NOD A-GA was used to tether the NODA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0196] NFE-NODA-GA contains a glutaric-acid (GA) spacer is short, purely aliphatic, and highly hydrophilic. This increases overall aqueous solubility and minimizes non-specific hydrophobic interactions compared with the more aromatic NH2-MPAA-NODA of Example 25, while retaining NODA’s fast, high-stability complexation.

[0197]

[0198] Formula XLIII

[0199] Example 27: As a further exemplary embodiment, a copolymer (Formula XLIV) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with p-NEE-Bn-NOTA was used to tether the NOTA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0200]

[0201] Example 28: As a further exemplary embodiment, a copolymer (Formula XLV) was synthesized with average repeat numbers x and y. A thiourea linkage along the backbone formed by coupling a pendant primary amine with p-NCS-benzyl-NODA-GA was used to tether the NODA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0202] The isothiocyanate handle enables extremely fast, high-yield conjugation via a hydrolytically robust thiourea bond. In addition, the glutaric-acid (GA) spacer attached to the NODA macrocycle increases hydrophilicity and reduces non-specific binding.

[0203]

[0204] Formula XLV

[0205] Example 29: As a further exemplary embodiment, a copolymer (Formula XLVI) was synthesized with average repeat numbers x and y. A single thiourea linkage along the backbone generated by reacting a pendant primary amine with NCS-MP-NODA was used to tether the NODA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0206] NCS-MP-NODA employs a minimal methylene-phenyl (MP) spacer. This shorter, less charged linker further decreases hydrodynamic size and can improve tumor penetration and clearance kinetics.

[0207]

[0208] Formula XLVI

[0209] Example 30: As a further exemplary embodiment, a copolymer (Formula XLVII) was synthesized with average repeat numbers x and y. A single amide linkage along the backbone formed by coupling a pendant primary amine with NOTA-NHS ester was used to tether the NOTA chelator, while the other chain end was functionalized with a cyclic RGD (cRGD) peptide.

[0210] The NHS-ester approach creates a hydrolytically stable amide bond, eliminating potential oxidation liabilities and simplifying regulatory acceptance. Example 31 : As a further exemplary embodiment, a copolymer (Formula XLVIII) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with NOTA-PEG-NEE was used to tether the NOTA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0211] Formula XLVIII

[0212] Example 32: As a further exemplary embodiment, a copolymer (Formula XLIX) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with NFE-MPA A-NOD A was used to tether the NODA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0213] Formula XLIX

[0214] Example 33: As a further exemplary embodiment, a copolymer (Formula L) was synthesized with average repeat numbers x and y. It bears an aryl dithiobenzoate residue at one chain end. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with

[0215] NH2-NODA-GA was used to tether the NODA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0216] The hydrophilic glutaric-acid spacer enhances aqueous solubility and minimizes non-specific hydrophobic interactions, promoting cleaner pharmacokinetics. In addition, the NODA core enables rapid, affording PET tracers of high specific activity under mild conditions.

[0217]

[0218] Formula L

[0219] Example 34: As a further exemplary embodiment, a copolymer (Formula LI) was synthesized with average repeat numbers x and y. A single carbamate linkage along the backbone formed by coupling a pendant carbonate-activated site with p-NEE-Bn-NOTA was used to tether the NOTA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide. NOTA enables a fast, furnishing PET probes with high specific activity and excellent in-vivo stability.

[0220]

[0221] Example 35: As a further exemplary embodiment, a copolymer (Formula LII) was synthesized with average repeat numbers x and y. A single thiourea linkage along the backbone formed by coupling a pendant primary amine with p-NCS-benzyl-NODA-GA was used to tether the NODA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide. The isothiocyanate handle enables very rapid, high-yield conjugation and furnishes a hydrolytically robust thiourea bond.

[0222]

[0223] Formula LII

[0224] Example 36:As a further exemplary embodiment, a copolymer (Formula LIII) was synthesized with average repeat numbers x and y. A thiourea linkage along the backbone formed by coupling a pendant primary amine with NCS-MP-NODA was used to tether the NODA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide.

[0225]

[0226] Formula LIII

[0227] Example 37: As a further exemplary embodiment, a copolymer (Formula LIV) was synthesized with average repeat numbers x and y. A single amide linkage along the backbone formed by coupling a pendant primary amine with NOTA-NHS ester was used to tether the NOTA chelator, while the other chain end was functionalized with an internalizing RGD (iRGD) peptide. This NHS-mediated amide bond is hydrolytically and oxidatively robust, and NOTA enables ultrafast, high-yield labeling under mild conditions, affording PET probes of high specific activity and excellent in-vivo stability.

[0228]

[0229] Formula LIV

Claims

CLAIMS1. A carrier platform functionalized with a chelating agent, wherein the carrier platform having the Formula I:MBDFormula I wherein,- ITP represents an integrin-targeting peptide that comprises cRGD, linear RGD or iRGD;- Pu is a polymeric unit;- MBD represents a metal-ion binding domain comprising at least one bifunctional chelating agent; and wherein the polymeric unit having the Formula II:wherein- x is a number between 15 and 300;- y is a number between 2 and 100; and- n is a number between 2 and 20.

2. The carrier platform according to claim 1, wherein the metal-ion binding domain further comprises at least one chelating agent that is selected from the group consisting of DFO, DOTA, CB-DO2A, 3p-C-DEPA, TCMC, DBCO, DIBO, BARAC, DIMAC, Oxo- DO3A, TE2A, CB-TE2A, CB-TE1A1P, CB-TE2P, MM-TE2A, DM-TE2A, diamsar, NODASA, NOD AGA, NOTA, NETA, TACN-TM, DTPA, 1B4M-DTPA, CHX-A"-DTPA, TRAP, NOPO, AAZTA, DATA, FFdedpa, FUoctapa, FFazapa, Hsdecapa, Ffcphospa, HBED, SHBED, BPCA, CP256, PCTA, HEHA, PEPA, EDTA, TETA, or TRITA.

3. The carrier platform according to claim 1 or claim 2 further comprising Li that is a first linker connecting the metal-ion binding domain to the polymer unit.

4. The carrier platform according to claim 3, wherein the polymeric unit having the FormulaIII:Formula III5. The carrier platform according to claim 3 or claim 4, wherein the first linker (Li) comprises at least one functional groups that is amide, carbamate and / or thiourea.

6. The carrier platform according to any one of claims 3 to 5, wherein the first linker (Li) is selected from the group consisting of:

7. The carrier platform according to claim 3 or claim 4, wherein the polymeric unit comprises two or more PEG units having the Formula IV:Formula IV wherein m is a number between 2 and 20.

8. The carrier platform according to any one of the claims 1 to 4, having the Formula V:wherein m is a number between 2 and 20.

9. The carrier platform according to any one of the claims 1 to 4, having the Formula VI:Formula VI10. The carrier platform according to any one of the claims 1 to 4, having the Formula VII:

11. The carrier platform according to any one of the claims 1 to 4, having the Formula VIII:

12. The carrier platform according to any one of the claims 1 to 4, having the Formula IX:Formula IX 13. The carrier platform according to any one of the claims 1 to 4, having the Formula X:Formula X wherein m is a number between 2 and 20.

14. The carrier platform according to any one of the claims 1 to 4, having the Formula XI:Formula XI15. The carrier platform according to any one of the claims 1 to 4, having the Formula XII:

16. The carrier platform according to any one of the claims 1 to 4, having the Formula XHI:

17. The carrier platform according to any one of the claims 1 to 4, having the Formula XIV:

18. The carrier platform according to any one of claims 1 to 4, having the Formula XV:Formula XV wherein m is a number between 2 and 20.

19. The carrier platform according to any one of the claims 1 to 4, having the Formula XVI:Formula XVI20. The carrier platform according to any one of the claims 1 to 4, having the Formula XVII:Formula XVII21. The carrier platform according to any one of the claims 1 to 4, having the Formula XVIII:

22. The carrier platform according to any one of the claims 1 to 4, having the Formula XIX:Formula XIX23. The carrier platform according to any one of the claims 1 to 4, having the Formula XX:

24. The carrier platform according to any one of the claims 1 to 4, having the Formula XXI:

25. The carrier platform according to any one of the claims 1 to 4, having the Formula XXII:wherein m is a number between 2 and 20.

26. The carrier platform according to any one of the claims 1 to 4, having the Formula XXIII:Formula XXIII 27. The carrier platform according to any one of the claims 1 to 4, having the Formula XXIV:Formula XXIV28. The carrier platform according to any one of the claims 1 to 4, having Formula XXV:

29. The carrier platform according to any one of the claims 1 to 4, having the Formula XXVI:Formula XXVI30. The carrier platform according to any one of the claims 1 to 4, having the Formula XXVII:

31. The carrier platform according to any one of the claims 1 to 4, having the Formula XXVIII:

32. The carrier platform according to any one of the preceding claims, further comprising one or more end group that is a polymerization initiator or a chain transfer agent that is a part of a trithiocarbonate or a dithioate.

33. The carrier platform according to claim 32, wherein the end group is selected from the group consisting of 3,5-Bis(2-dodecylthiocarbonothioylthio-l-oxopropoxy)benzoic acid, 3 -Butenyl 2-(dodecylthiocarbonothioylthio)-2-methylpropionate, 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid, 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol, Cyanomethyl dodecyl, Cyanomethyl [3- (trimethoxysilyl)propyl] trithiocarbonate, 2-Cyano-2-propyl dodecyl trithiocarbonate, S,S- Dibenzyl trithiocarbonate, 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid N-hydroxysuccinimide ester, 2- (Dodecylthiocarbonothioylthio)-2-methylpropionic acid pentafluorophenyl ester, 2- (Dodecylthiocarbonothioylthio)propionic acid, Methyl 2-(dodecylthiocarbonothioylthio)- 2-methylpropionate, Pentaerythritol tetrakis[2-(dodecylthiocarbonothioylthio)-2- methylpropionate], Phthalimidomethyl butyl trithiocarbonate, 1,1,1- Tris[(dodecylthiocarbonothioylthio)-2-methylpropionate]ethane, benzyl benzodithioate,Cyanomethyl benzodithioate, 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid, 4- Cyano-4-(phenylcarbonothioylthio)pentanoic acid N-succinimidyl ester, 2-Cyano-2- propyl benzodithioate, 2-Cyano-2-propyl 4-cyanobenzodithioate, Ethyl 2-(4- methoxyphenylcarbonothioylthio)acetate, Ethyl 2-methyl-2-(phenylthiocarbonylthio)propionate, Ethyl 2-(phenylcarbonothioylthio)-2-phenylacetate, Ethyl 2-(phenylcarbonothioylthio)propionate, 1 -(Methoxy carbonyl)ethyl benzodithioate, 2-(4-Methoxyphenylcarbonothioylthio)ethanoic acid, 4-cyano-4-(phenylcarbonothioylthio)pentanoate, 2-(Phenylcarbonothioylthio)propanoic acid, 2- Phenyl-2-propyl benzodithioate, Cyanomethyl methyl(4-pyridyl)carbamodithioate, Cyanopropan-2-yl N-methyl-N-(pyridin-4-yl)carbamodithioate, Methyl 2-[methyl(4- pyridinyl)carbamothioylthio]propi onate or l-Succinimidyl-4-cyano-4-[N-methyl-N-(4- pyridyl)carbamothioylthio]pentanoate.

34. A complex comprising the carrier platform defined in any one of the preceding claims or a pharmaceutically acceptable salt thereof, and an ion of a stable form of a metal selected from a group consisting of Ga, Lu, Cu, Ac, Y or Zr.

35. The complex comprising the carrier platform defined in any one of the claims 1 to 33, or a pharmaceutically acceptable salt thereof, and an ion of a radionuclide selected from a group consisting of Ga, Lu, Cu, Ac, Y or Zr.

36. The complex comprising the carrier platform defined in any one of the claims 1 to 33 or a pharmaceutically acceptable salt thereof, and an ion of Gd.

37. The carrier platform according to any one of the claims 1 to 33 further comprising at least one metal selected the group of consisting of Zr-89, Ac-225, Y-90, Lu- 177, Ga-68, Cu-64, Cu-67, or Gd-157.

38. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables the imaging of the cancer cells, wherein said radionuclide is Ga-68.

39. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables the destruction of the cancer cells, wherein said radionuclide is Lu- 177.

40. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables imaging of cancer cells, wherein said radionuclide is Zr-89.

41. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables imaging of cancer cells, wherein said radionuclide is Cu-64.

42. The carrier platform according to any one of the claims 1 to 33, further comprising a metal which enables imaging of cancer cells, wherein said metal is Gd-157.

43. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Ac- 225.

44. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Y-90.

45. The carrier platform according to any one of the claims 1 to 33, further comprising a radionuclide which enables destruction of cancer cells, wherein said radionuclide is Cu-67.

46. A theranostic kit comprising: a) a carrier platform or a complex according to any one of the preceding claims, b) at least one radionuclide-including compound configured for imaging cancer cells or monitoring cancer progression.

47. The theranostic kit according to claim 46 comprising at least one radionuclide-including compound configured for the targeted treatment of cancer cells.

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