Nectin-4 ligands

Abstract

According to the invention, a compound of the general formula I is provided.

Description

The invention relates to peptide-based Nectin-4 ligands, in particular radiolabeled Nectin-4 ligands. It further relates to the use of Nectin-4 ligands for the production of radiopharmaceuticals. Approximately 18,270 people in Germany were diagnosed with invasive bladder cancer (also known as muscle-invasive bladder carcinoma) in 2018, roughly a quarter of whom were women. Around 5,600 people died from the disease (RKI, Center for Cancer Registry Data). Bladder cancer is predominantly urothelial carcinoma, which often occurs simultaneously in various locations within the bladder and urinary tract. Following diagnosis, treatment depends on the stage of the disease and includes surgical removal of the tumor, including removal of the bladder, as well as neoadjuvant and adjuvant chemotherapy (including immunotherapy). For patients with metastatic urothelial carcinoma, the antibody-drug conjugate enfortumab vedotin (“EV,” Padcev) has been FDA-approved and EMA-approved since 2019 and 2022, respectively, as a targeted therapy. The antibody component of Padcev targets the cell surface protein Nectin-4.Upon binding, the Nectin-4-EV complex is internalized and the toxin monomethyl auristatin E is released via proteolytic cleavage. This toxin then exerts a cytotoxic effect by inhibiting tubulin polymerization.1 In a recent study, it was shown that 72 of 83 (87%) tumor samples of non-muscle-invasive bladder cancer and 50 of 86 (58%) tumor samples of muscle-invasive bladder cancer were Nectin-4 positive.2 These results, along with its low prevalence in healthy tissue and its location on the cell surface, underscore the suitability of Nectin-4 as a biological target for radiolabeled ligands, or radioligands.3 Inspired by Padcev, Bicycle Therapeutics developed the bicyclic toxin conjugate BT8009 (zelenectide pevedotin). While the linker and toxin unit are similar to Padcev, the Nectin-4 binding unit is a bicyclic peptide identified by phage display and subsequently systematically optimized.5,6 BT8009 is currently in phase I / II clinical trials in patients with solid tumors and elevated Nectin-4 levels, including patients with urothelial neoplasms (clinical trial: NCT04561362). Little is known about radioligands for Nectin-4. Two studies have developed antibody-based radioligands for imaging using PET (positron emission tomography, labeled with fluorine-18 or zirconium-897) and SPECT (single-photon emission computed tomography, labeled with technetium-99m8). Furthermore, a peptide-based radioligand based on BT8009 (bicyclic radiopeptide conjugate 68Ga-N188) was reported, in which the linker and toxin units were replaced by the radiometallic chelator DOTA and gallium-68 was used as the diagnostic radionuclide.9,10 In addition to preclinical evaluation in mice, the first patients with metastatic urothelial carcinoma and other cancers were also subjected to PET imaging after injection of 68Ga-N188 (clinical studies: NCT05321316 and NCT05593107).Three recently published studies described the development and preclinical investigation of derivatives of 68Ga-N188 (NOTA-PEGn-BP, DN68, FZ-NR-1-3).11,12,13 These studies involved modifications to the peptide backbone and chelator unit, as well as the testing of different linkers between the chelator unit and the peptide. Additionally, studies have reported on 18F-labeled ligands (N230-232).14 Structural information on BT8009, N188, and its derivatives is presented in Table 1 below. Despite positive results in preclinical and clinical studies, 68Ga-N188 still has clear potential for improvement. Firstly, its binding affinity to Nectin-4 (Kd = 23.7 nM) could be improved, especially considering the advent of whole-body PET / CT scanners for humans (i.e., large axial field of view (LAFOV) PET / CT). Secondly, the observed tumor uptake, and particularly the resulting tumor-to-muscle and tumor-to-blood ratios, are only moderately satisfactory.9,10 It is likely that the latter is also due to the moderate binding affinity of the radioligand to Nectin-4. Radioligands targeting other tumor antigens, especially those targeting PSMA and SST2, typically exhibit binding affinities in the single-digit nM range or below. The binding affinities of the NOTA-PEGn-BP compounds also do not appear to be improved,11 while DN68, with a Kd value of 0.64 nM, is significantly more potent.12 From a (radio)chemical perspective, all known radioligands share another disadvantage. Similar to BT8009, these compounds contain a methionine residue at position 4 of the bicyclic core. Methionine residues exhibit a certain susceptibility to oxidation, which oxidizes the methyl sulfide group to the corresponding methyl sulfoxide group (Fig. 2A).15 This can result in undesirable byproducts during the synthesis of non-radioactive peptides and also during radiolabeling. In the case of peptide synthesis, this leads to yield losses, and in the case of radiolabeling, to reduced radiochemical purity. Furthermore, oxidation can lead to altered binding behavior with the corresponding protein.15 It is therefore desirable to develop novel peptide ligands that target tumor-associated Nectin-4 for the functional characterization of tumor diseases and can be labeled with radionuclides to enable non-invasive molecular imaging, particularly using PET. Furthermore, these peptide ligands should possess greater binding affinity and improved tumor uptake, as well as be less susceptible to oxidation. In particular, high yields, low energy consumption, and the use of cost-effective raw materials should be achieved. Bicyclic peptide ligands are known from WO 2023 / 098072 A1 and WO 2023 / 031623 A2 which have a methionine residue at position 4 of the bicyclic core and are able to bind Nectin-4. The object of the invention is to eliminate the disadvantages of the prior art. In particular, peptide ligands exhibiting the aforementioned properties are to be specified. This problem is solved by the features of claims 1, 8, 9 and 11. Advantageous embodiments of the inventions result from the features of the dependent claims. According to the invention, a compound of the general formula I provided for, whereby <row> <cell> Y< / cell> <cell> <figure xml:id="_e747390043" n="0001" type="chem" style="portrait" facs="0003"> <graphic height="9" width="60" source="DE102025117507B3_0004.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0004" / > <media mimeType="image / tif" url="DE102025117507B3_0004.tif" / > < / figure> or <figure xml:id="_e747390044" n="0001" type="chem" style="portrait" facs="0004"> <graphic height="8" width="28" source="DE102025117507B3_0005.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0005" / > <media mimeType="image / tif" url="DE102025117507B3_0005.tif" / > < / figure> is;< / cell> < / row> <row> <cell> X< / cell> <cell>selected from the group consisting of O, Se and CH <hi rend="subscript"> 2< / hi> consists;< / cell> < / row> <row> <cell> D< / cell> <cell>1-Naphthyl (D1) or 2-Naphthyl (D2) is;< / cell> < / row> <row> <cell> L< / cell> <cell> selected from the group consisting of< / cell> < / row> <title desc="title">< / title> <row> <cell> <figure xml:id="_e747390064" n="0001" type="chem" style="portrait" facs="0005"> <graphic height="68" width="62" source="DE102025117507B3_0006.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0006" / > <media mimeType="image / tif" url="DE102025117507B3_0006.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390066" n="0001" type="chem" style="portrait" facs="0006"> <graphic height="18" width="46" source="DE102025117507B3_0007.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0007" / > <media mimeType="image / tif" url="DE102025117507B3_0007.tif" / > < / figure> < / cell> < / row> <row> <cell> L2< / cell> < / row> <row> <cell> <figure xml:id="_e747390071" n="0001" type="chem" style="portrait" facs="0007"> <graphic height="19" width="39" source="DE102025117507B3_0008.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0008" / > <media mimeType="image / tif" url="DE102025117507B3_0008.tif" / > < / figure> < / cell> < / row> <row> <cell> L3< / cell> < / row> <row> <cell> <figure xml:id="_e747390076" n="0001" type="chem" style="portrait" facs="0008"> <graphic height="12" width="48" source="DE102025117507B3_0009.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0009" / > <media mimeType="image / tif" url="DE102025117507B3_0009.tif" / > < / figure> < / cell> < / row> <row> <cell> L1< / cell> <cell> L4< / cell> < / row> <row> <cell> <figure xml:id="_e747390082" n="0001" type="chem" style="portrait" facs="0009"> <graphic height="20" width="54" source="DE102025117507B3_0010.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0010" / > <media mimeType="image / tif" url="DE102025117507B3_0010.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390084" n="0001" type="chem" style="portrait" facs="0010"> <graphic height="18" width="25" source="DE102025117507B3_0011.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0011" / > <media mimeType="image / tif" url="DE102025117507B3_0011.tif" / > < / figure> < / cell> < / row> <row> <cell> L5< / cell> <cell> L6< / cell> < / row> <row> <cell> <figure xml:id="_e747390090" n="0001" type="chem" style="portrait" facs="0011"> <graphic height="62" width="58" source="DE102025117507B3_0012.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0012" / > <media mimeType="image / tif" url="DE102025117507B3_0012.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390092" n="0001" type="chem" style="portrait" facs="0012"> <graphic height="15" width="17" source="DE102025117507B3_0013.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0013" / > <media mimeType="image / tif" url="DE102025117507B3_0013.tif" / > < / figure> < / cell> < / row> <row> <cell> L8< / cell> <cell> L7< / cell> < / row> <lb / > consists; <lb / > A is selected from the group consisting of <title desc="title">< / title> <row> <cell> <figure xml:id="_e747390109" n="0001" type="chem" style="portrait" facs="0013"> <graphic height="39" width="46" source="DE102025117507B3_0014.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0014" / > <media mimeType="image / tif" url="DE102025117507B3_0014.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390111" n="0001" type="chem" style="portrait" facs="0014"> <graphic height="41" width="37" source="DE102025117507B3_0015.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0015" / > <media mimeType="image / tif" url="DE102025117507B3_0015.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390113" n="0001" type="chem" style="portrait" facs="0015"> <graphic height="43" width="46" source="DE102025117507B3_0016.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0016" / > <media mimeType="image / tif" url="DE102025117507B3_0016.tif" / > < / figure> < / cell> < / row> <row> <cell> A1< / cell> <cell> A2< / cell> <cell> A3< / cell> < / row> <row> <cell> <figure xml:id="_e747390120" n="0001" type="chem" style="portrait" facs="0016"> <graphic height="43" width="45" source="DE102025117507B3_0017.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0017" / > <media mimeType="image / tif" url="DE102025117507B3_0017.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390122" n="0001" type="chem" style="portrait" facs="0017"> <graphic height="56" width="45" source="DE102025117507B3_0018.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0018" / > <media mimeType="image / tif" url="DE102025117507B3_0018.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390124" n="0001" type="chem" style="portrait" facs="0018"> <graphic height="44" width="32" source="DE102025117507B3_0019.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0019" / > <media mimeType="image / tif" url="DE102025117507B3_0019.tif" / > < / figure> < / cell> < / row> <row> <cell> A4< / cell> <cell> A5< / cell> <cell> A6< / cell> < / row> <row> <cell> <figure xml:id="_e747390131" n="0001" type="chem" style="portrait" facs="0019"> <graphic height="19" width="27" source="DE102025117507B3_0020.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0020" / > <media mimeType="image / tif" url="DE102025117507B3_0020.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390133" n="0001" type="chem" style="portrait" facs="0020"> <graphic height="37" width="77" source="DE102025117507B3_0021.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0021" / > <media mimeType="image / tif" url="DE102025117507B3_0021.tif" / > < / figure> < / cell> < / row> <row> <cell> A7< / cell> <cell> A8< / cell> < / row> <row> <cell> <figure xml:id="_e747390139" n="0001" type="chem" style="portrait" facs="0021"> <graphic height="18" width="25" source="DE102025117507B3_0022.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0022" / > <media mimeType="image / tif" url="DE102025117507B3_0022.tif" / > < / figure> < / cell> <cell> <figure xml:id="_e747390141" n="0001" type="chem" style="portrait" facs="0022"> <graphic height="18" width="25" source="DE102025117507B3_0023.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0023" / > <media mimeType="image / tif" url="DE102025117507B3_0023.tif" / > < / figure> < / cell> < / row> <row> <cell> A9< / cell> <cell> A10< / cell> < / row> <p xml:id="_e747390145" n="0012">exists; R <hi rend="superscript"> 1< / hi> selected from the group consisting of H, F, Cl, Br, I, -CF <hi rend="subscript"> 3< / hi> , -CH <hi rend="subscript"> 3< / hi> , -OH and -OCH <hi rend="subscript"> 3< / hi> exists; R <hi rend="superscript"> 2< / hi> -OH or -NH <hi rend="subscript"> 2< / hi> is; Z CH or N is; m is 0 or 1; n is 0 or 1 and p is an integer between 1 and 10. <p xml:id="_e747390152" n="0013"> The compounds of general formula I are peptide ligands, specifically Nectin-4 ligands. It is possible to label these Nectin-4 ligands with a radionuclide, making them suitable for the functional characterization of cancers using positron emission tomography (PET) and single-photon emission computed tomography (SPECT).<p xml:id="_e747390153" n="0014">According to the invention, Y in the compounds of general formula I can be Y1, Y2, or Y3. It can further be provided that Y in the compounds of general formula I is Y2. It can also be provided that X in the compounds of general formula IO, Se, or CH <hi rend="subscript"> 2< / hi> XO or CH is preferred. <hi rend="subscript"> 2< / hi> X O is particularly preferred. <p xml:id="_e747390156" n="0015"> According to the invention, A is selected from the group consisting of A1, A2, A3, A4, A5, A6, A7, A8, A9, or A10. Preferably, A is selected from the group consisting of A1, A2, A3, A6, and A9. More preferably, A is selected from the group consisting of A1, A6, and A9. Particularly preferably, A is A1. <p xml:id="_e747390157" n="0016"> According to the invention, L is selected from the group consisting of L1, L2, L3, L4, L5, L6, L7 and L8. Preferably, L is selected from the group consisting of L2, L3, L5 and L8. Particularly preferred is L2 or L3, and even more preferably L2. <p xml:id="_e747390158" n="0017">According to the invention, n can be 0 or 1. Preferably, n is equal to 0. <p xml:id="_e747390159" n="0018"> According to the invention, m can be 0 or 1. Preferably, m is equal to 1. <p xml:id="_e747390160" n="0019"> According to the invention, D in the compounds of general formula I can be D1 or D2. Preferably, D is D1. <p xml:id="_e747390161" n="0020">According to the invention, a compound of general formula I is preferred, in which Y is Y2, XO or CH <hi rend="subscript"> 2< / hi> is, A A1 is, L L2, L3 or is not present, D D1 is and m 1 is. <p xml:id="_e747390163" n="0021">Preferred examples of a compound of general formula I are: <title desc="title">< / title> <row> <cell> TKR2-14< / cell> <cell> <figure xml:id="_e747390174" n="0001" type="chem" style="portrait" facs="0023"> <graphic height="109" width="129" source="DE102025117507B3_0024.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0024" / > <media mimeType="image / tif" url="DE102025117507B3_0024.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR2-24< / cell> <cell> <figure xml:id="_e747390178" n="0001" type="chem" style="portrait" facs="0024"> <graphic height="109" width="129" source="DE102025117507B3_0025.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0025" / > <media mimeType="image / tif" url="DE102025117507B3_0025.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR2-80< / cell> <cell> <figure xml:id="_e747390182" n="0001" type="chem" style="portrait" facs="0025"> <graphic height="110" width="125" source="DE102025117507B3_0026.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0026" / > <media mimeType="image / tif" url="DE102025117507B3_0026.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR2-84< / cell> <cell> <figure xml:id="_e747390186" n="0001" type="chem" style="portrait" facs="0026"> <graphic height="84" width="127" source="DE102025117507B3_0027.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0027" / > <media mimeType="image / tif" url="DE102025117507B3_0027.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-08< / cell> <cell> <figure xml:id="_e747390190" n="0001" type="chem" style="portrait" facs="0027"> <graphic height="113" width="127" source="DE102025117507B3_0028.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0028" / > <media mimeType="image / tif" url="DE102025117507B3_0028.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-18< / cell> <cell> <figure xml:id="_e747390194" n="0001" type="chem" style="portrait" facs="0028"> <graphic height="110" width="125" source="DE102025117507B3_0029.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0029" / > <media mimeType="image / tif" url="DE102025117507B3_0029.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-30< / cell> <cell> <figure xml:id="_e747390198" n="0001" type="chem" style="portrait" facs="0029"> <graphic height="86" width="128" source="DE102025117507B3_0030.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0030" / > <media mimeType="image / tif" url="DE102025117507B3_0030.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-34< / cell> <cell> <figure xml:id="_e747390202" n="0001" type="chem" style="portrait" facs="0030"> <graphic height="85" width="124" source="DE102025117507B3_0031.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0031" / > <media mimeType="image / tif" url="DE102025117507B3_0031.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-42< / cell> <cell> <figure xml:id="_e747390206" n="0001" type="chem" style="portrait" facs="0031"> <graphic height="95" width="97" source="DE102025117507B3_0032.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0032" / > <media mimeType="image / tif" url="DE102025117507B3_0032.tif" / > < / figure> < / cell> < / row> <row> <cell> TKR3-46< / cell> <cell> <figure xml:id="_e747390210" n="0001" type="chem" style="portrait" facs="0032"> <graphic height="59" width="131" source="DE102025117507B3_0033.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0033" / > <media mimeType="image / tif" url="DE102025117507B3_0033.tif" / > < / figure> < / cell> < / row> <p xml:id="_e747390211" n="0022">Compound TKR2-14 is a compound of general formula I, where D is D1, Y is Y2, X is CH <hi rend="subscript"> 2< / hi> is, m is 1, n is 0 and A is A1. <p xml:id="_e747390213" n="0023"> Compound TKR2-24 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 0 and A is A1. <p xml:id="_e747390214" n="0024"> Compound TKR2-80 is a compound of general formula I, where D is D1, Y is Y1, XO is, m is 1, n is 0 and A is A1. <p xml:id="_e747390215" n="0025"> Compound TKR2-84 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 1, L is L5 with p = 2 and A is A6. <p xml:id="_e747390216" n="0026"> Compound TKR3-08 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 1, L is L8 with p = 1 and A is A1. <p xml:id="_e747390217" n="0027"> Compound TKR3-18 is a compound of general formula I, where D is D1, Y is Y3, m is 1, n is 0 and A is A1. <p xml:id="_e747390218" n="0028">Compound TKR3-30 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 1, L is L2 with p = 1 and A is A1. <p xml:id="_e747390219" n="0029"> Compound TKR3-34 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 1, L is L2 with p = 7 and A is A1. <p xml:id="_e747390220" n="0030"> Compound TKR3-42 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 0 and A is A9 with Z = N. <p xml:id="_e747390221" n="0031"> Compound TKR3-46 is a compound of general formula I, where D is D1, Y is Y2, XO is, m is 1, n is 1, L is L3 with p = 10 and A is A1. <p xml:id="_e747390222" n="0032">In one embodiment of the present one, in the compounds of general formula I, if A is A9, F [ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> -< / hi> and if A is A10; I [ <hi rend="superscript"> 123< / hi> I]I <hi rend="superscript"> -< / hi> , [ <hi rend="superscript"> 124< / hi> I]I <hi rend="superscript"> -< / hi> , [ <hi rend="superscript"> 125< / hi> I]I <hi rend="superscript"> -< / hi> , [ <hi rend="superscript"> 131< / hi> I]I <hi rend="superscript"> -< / hi> , preferred [ <hi rend="superscript"> 123< / hi> I]I <hi rend="superscript"> -< / hi> . <p xml:id="_e747390235" n="0033">According to the invention, a complex is further provided consisting of a compound of general formula I, wherein A is A1 to A8, and a radioactive metal ion or A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> consists. <p xml:id="_e747390238" n="0034">It may be provided that the radioactive metal ion of the complex is selected from the group consisting of [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 177< / hi> Lu]Lu <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 149< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 155< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 152< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 161< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 225< / hi> Ac]Ac <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 226< / hi> Ac]Ac <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 132< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 135< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 111< / hi> In]In <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 86< / hi> Y]Y <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 90< / hi> Y]Y <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 212< / hi> Bi]Bi <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 213< / hi> Bi]Bi <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 43< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 44< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 47< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 203< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 212< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> consists. <p xml:id="_e747390289" n="0035">It may be provided that the complex consists of a compound of the general formula I, where A is A1, and A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 43< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 44< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 47< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> , preferably A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , especially preferred [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> consists. <p xml:id="_e747390318" n="0036">It may be provided that the complex consists of a compound of the general formula I, where A is A2, and A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 43< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 44< / hi> Sc]Sc <hi rend="superscript"> 3< / hi> , [ <hi rend="superscript"> 47< / hi> Sc]Sc <hi rend="superscript"> 3+< / hi> preferably A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , especially preferred [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> consists. <p xml:id="_e747390347" n="0037">It may be provided that the complex consists of a compound of the general formula I, where A is A3, and [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 177< / hi> Lu]Lu <hi rend="superscript"> 3+< / hi> , [14 <hi rend="superscript"> 9< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 155< / hi> [Tb] Tb <hi rend="superscript"> 3+< / hi> [ <hi rend="superscript"> 152< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 161< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 225< / hi> Ac]Ac <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 226< / hi> Ac]Ac <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 132< / hi> La]La <hi rend="superscript"> 3+< / hi> [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 135< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 111< / hi> In]In <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 86< / hi> Y]Y <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 90< / hi> Y]Y <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 212< / hi> Bi]Bi <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 213< / hi> Bi]Bi <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 43< / hi> SC]SC <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 44< / hi> SC]SC <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 47< / hi> SC]SC <hi rend="superscript"> 3+< / hi> [ <hi rend="superscript"> 203< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 212< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> preferably [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 64< / hi> With]With <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , particularly preferred [ <hi rend="superscript"> 64< / hi> With]With <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> exists. <p xml:id="_e747390408" n="0038">It may be provided that the complex consists of a compound of the general formula I, where A is A4, and A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> consists. <p xml:id="_e747390411" n="0039">It may be provided that the complex consists of a compound of the general formula I, where A is A5, and [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> preferably [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> consists. <p xml:id="_e747390420" n="0040">It may be provided that the complex consists of a compound of the general formula I, where A is A6, and A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 67< / hi> Ga] Ga <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 111< / hi> In]In <hi rend="superscript"> 3+< / hi> , preferably A1[ <hi rend="superscript"> 18< / hi> F]F <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> , especially preferred [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> consists. <p xml:id="_e747390435" n="0041">It may be provided that the complex consists of a compound of the general formula I, where A is A7, and [ <hi rend="superscript"> 61< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> , [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 67< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> preferably [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> consists. <p xml:id="_e747390444" n="0042">It may be provided that the complex consists of a compound of the general formula I, where A is A8; and [ <hi rend="superscript"> 177< / hi> Lu]Lu <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 149< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 155< / hi> Tb ]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 152< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 161< / hi> [Tb]Tb <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 225< / hi> AC]AC <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 226< / hi> Ac]Ac <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 132< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 135< / hi> La]La <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 212< / hi> Bi]Bi <hi rend="superscript"> 3+< / hi> , [ <hi rend="superscript"> 213< / hi> B1]B <hi rend="superscript"> 13+< / hi> , [ <hi rend="superscript"> 203< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 212< / hi> Pb]Pb <hi rend="superscript"> 3+< / hi> preferably [ <hi rend="superscript"> 225< / hi> Ac ]Ac <hi rend="superscript"> 3+< / hi> or [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> , especially preferred [ <hi rend="superscript"> 133< / hi> La]La <hi rend="superscript"> 3+< / hi> consists. <p xml:id="_e747390479" n="0043">Particularly preferred is a complex consisting of a compound of the general formula I, where A is A1, and [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> . <p xml:id="_e747390484" n="0044">A complex consisting of a compound of general formula I, in which Y is Y2, XO or CH is particularly preferred. <hi rend="subscript"> 2< / hi> is, A A1 is, L L2, L3 or is not present, D D1 is and m 1 is, and [ <hi rend="superscript"> 64< / hi> Cu]Cu <hi rend="superscript"> 2+< / hi> or [ <hi rend="superscript"> 68< / hi> Ga]Ga <hi rend="superscript"> 3+< / hi> . <p xml:id="_e747390490" n="0045"> The compounds of general formula I can be combined by coupling a compound of general formula II <figure xml:id="_e747390491" n="0001" type="chem" style="portrait" facs="0033"> <graphic height="92" width="80" source="DE102025117507B3_0034.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0034" / > <media mimeType="image / tif" url="DE102025117507B3_0034.tif" / > < / figure> <lb / > to a compound of general formula III <figure xml:id="_e747390493" n="0001" type="chem" style="portrait" facs="0034"> <graphic height="23" width="173" source="DE102025117507B3_0035.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0035" / > <media mimeType="image / tif" url="DE102025117507B3_0035.tif" / > < / figure> <lb / > or a combination of the general formula IV <figure xml:id="_e747390495" n="0001" type="chem" style="portrait" facs="0035"> <graphic height="30" width="173" source="DE102025117507B3_0036.tif" url=" / c6c9662d-3825-4197-8c8d-9a04de317da5_DE102025117507B3_0036" / > <media mimeType="image / tif" url="DE102025117507B3_0036.tif" / > < / figure> <lb / > The compounds are obtained using O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU). The coupling is preferably carried out under oscillating mixing. <p xml:id="_e747390497" n="0046">The compounds of general formula II are hereinafter also referred to as peptides according to the invention. The peptides according to the invention can be synthesized by automated microwave-assisted solid-phase peptide synthesis (SPPS) using an initiator, Astra, from Biotage. Fmoc-Rink-amide resin can be used as the starting material. Using an automated microwave peptide synthesizer and repeated cycles of Fmoc removal (piperidine / DMF) and coupling (HATU / DIPEA / DMF), the peptides can be built up. Subsequently, the peptides according to the invention can be manually coupled (HATU / DIPEA / DMF) with chelators or other compounds suitable for radiosynthesis. Afterward, they are cleaved from the resin, and all protecting groups are removed by treatment with TFA / H. <hi rend="subscript"> 2< / hi> O / TIPS and, after removal of TFA, the peptides are precipitated with ice-cold diethyl ether. The linear peptide is dissolved in a mixture of acetonitrile and water and treated with NH₃. <hi rend="subscript"> 4< / hi> HCO <hi rend="subscript"> 3< / hi> (100 mM) diluted. TCEP was added to the solution. The reaction was initiated by adding TATA. After completion of the reaction, the pH was adjusted to 2.0 with TFA / water. The solution was then lyophilized and purified by RP-HPLC. <p xml:id="_e747390501" n="0047">The compounds of general formula I according to the invention can be used as medicaments for the diagnosis and treatment of diseases involving the cell surface protein Nectin-4. The medicament is preferably a medicament for the diagnosis and treatment of bladder cancer and breast cancer. <p xml:id="_e747390502" n="0048"> The compounds of general formula I according to the invention can be used in the production of radiopharmaceuticals. Details of the production of the radiopharmaceuticals are explained in more detail in the Examples section. <p xml:id="_e747390503" n="0049">Unless otherwise specified, the term "alkyl" refers in particular to a saturated aliphatic hydrocarbon group having a branched or unbranched carbon chain with 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, and particularly preferably 1 to 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, n-hexyl, octyl, dodecyl, and the like. The alkyl group may optionally be substituted with one or more substituents. <p xml:id="_e747390504" n="0050"> The term “acyl” refers to a group of the formula -C(O)-R, where R is alkyl as defined herein.<p xml:id="_e747390505" n="0051">The invention is explained in more detail below with reference to exemplary embodiments that are not intended to limit the invention and to the drawings. <list xml:id="_e747390506" type="bulleted"> <item>Fig. 1 Cell binding and internalization of the <hi rend="superscript"> 64< / hi> Cu-labeled compounds TKR2-08 (reference compound), TKR2-14, TKR2-24, TKR2-80, TKR3-08, TKR3-18, TKR3-30, TKR3-34, TKR3-40 and TKR3-46 on Nectin-4-positive (HT-1376) and Nectin-4-negative (5637) cells;< / item> <item>Fig. 2 Cell binding and internalization of the <hi rend="superscript"> 68< / hi> Ga-labeled compounds TKR2-08, TKR2-24 and TKR2-52 (corresponding to prior art compound N188) on Nectin-4-positive (HT-1376) and Nectin-4-negative (5637) cells;< / item> <item>Fig. 3 Saturation binding curves of the <hi rend="superscript"> 64< / hi> Cu-labeled compounds TKR2-08 (A), TKR2-24 (B), TKR3-08 (C), TKR3-34 (D) and TKR3-46 (E);< / item> <item>Fig. 4 Saturation binding curves of the <hi rend="superscript"> 68< / hi> Ga-labeled compounds TKR2-08 (A), TKR2-52 (=N188) (B) and TKR2-24 (C);< / item> <item>Fig. 5 Time-dependent SUV curves for the uptake of radioligands in HT-1376 tumors (A) and the time courses of the tumor-to-muscle (B), tumor-to-heart (C), tumor-to-kidney (D) and tumor-to-liver (E) ratios for the <hi rend="superscript"> 64< / hi> Cu-labeled compounds TKR2-08, TKR2-14, TKR2-24, TKR3-08, TKR3-34 and TKR3-46 in tumor-bearing mice;< / item> <item>Fig. 6 Time-dependent SUV curves for the uptake of radioligands in HT-1376 tumors (A) and the time courses of the tumor-to-muscle (B), tumor-to-heart (C), tumor-to-kidney (D) and tumor-to-liver (E) ratios for the <hi rend="superscript"> 68< / hi> Ga-labeled compounds TKR2-08, TKR2-52 (=N188) and TKR2-24 in tumor-bearing mice;< / item> <item>Fig. 7 analytical radio-HPLC chromatograms according to <hi rend="superscript"> 64< / hi> Cu- or <hi rend="superscript"> 68< / hi> Ga marking: [ <hi rend="superscript"> 64< / hi> Cu]Cu-TKR2-08 with evidence that the resulting impurity during radiolabeling is the corresponding peptide with methionine sulfoxide residue (A), [ <hi rend="superscript"> 64< / hi> Cu]Cu-TKR2-24 (B), [ <hi rend="superscript"> 68< / hi> Ga]Ga-TKR2-08 where magnification also shows the formation of the corresponding sulfoxide (C), [ <hi rend="superscript"> 68< / hi> Ga]Ga-TKR2-52 where magnification also shows the formation of the corresponding sulfoxide (D) and< / item> <item>Fig. 8 time-dependent degradation of the <hi rend="superscript"> 64< / hi> Cu-labeled ligands TKR2-08, TKR2-24, TKR2-44 and TKR2-50 by incubation in 0.001% H <hi rend="subscript"> 2< / hi> O <hi rend="subscript"> 2< / hi> -Solution.< / item> < / list> Example 1: Synthesis of TKR2-24 <p xml:id="_e747390532" n="0052">The compound TKR2-24 was synthesized by automated microwave-assisted solid-phase peptide synthesis (SPPS) using Biotage's Astra initiator. Fmoc rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g) was used as the starting material and swelled in DMF (2 ml / 0.1 mmol) under oscillating mixing and microwave heating (70 °C) for 30 min. Fmoc removal was performed using two cycles of 20% piperidine in DMF containing 0.1 M HOBt (2 mL, 2 mL / 0.1 mmol), each for 10 min. The resin was washed twice with DMF and HATU (152 mg, 0.4 mmol, 4 eq., 0.5 M in DMF), followed by the addition of DIPEA (68 mL, 0.8 mmol, 8 eq., 2 M in N-methyl-2-pyrrolidinone (NMP)) and Fmoc-L-Cys(Trt)-OH (234 mg, 0.4 mmol, 4 eq., 0.2 M in DMF). Coupling was carried out under oscillating mixing at room temperature for 60 min. The resin was then washed twice with DMF, followed by another cycle of Fmoc removal as described above. HATU (152 mg, 0.4 mmol, 4 eq., 0.5 M in DMF), DIPEA (68 ml, 0.8 mmol, 8 eq., 2 M in N-Methyl-2-pyrrolidinone (NMP)) and Fmoc-L-Trp(Boc)-OH (211 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) were added. Coupling was performed under oscillating mixing and microwave heating (75 °C) for 5 min. Further peptide fusion was achieved by alternating cycles of Fmoc removal and amino acid coupling with Fmoc-L-Cys(Trt)-OH and Fmoc-L-HArg(Pbf)-OH, which were coupled at room temperature for 60 min, and Fmoc-L-Hyp(tBu)-OH, Fmoc-L-Pro-OH, Fmoc-D-Asp(tBu)-OH, Fmoc-L-Ser(tBu)-OH, Fmoc-L-Trp(Boc)-OH, Fmoc-L-Thr(tBu)-OH, Fmoc-L-Mox-OH, Fmoc-L-Asp(tBu)-OH and Fmoc-1NaI-OH, which were coupled under microwave heating (75 °C) for 5 min. After coupling of the last Fmoc-L-Cys(Trt)-OH, another cycle of Fmoc removal was performed and the resin was washed twice with DMF. <p xml:id="_e747390533" n="0053">(R)-NO-DAGA(tBu) was added to the swollen resin (0.025 mmol) in DMF (2 ml / 0.1 mmol). <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 ml, 4 eq.) and HATU (19 mg, 0.05 mmol, 1 eq., 0.5 M in DMF) were added. The mixture was shaken for 12 h. The resin was treated with DMF, CH <hi rend="subscript"> 2< / hi> Cl <hi rend="subscript"> 2< / hi> , CH <hi rend="subscript"> 3< / hi> The resin was washed with OH and diethyl ether (twice each). It was then dried in an oven at 50 °C for 30 minutes. <p xml:id="_e747390538" n="0054">TIPS (125 ml) and H were added to the dry resin (0.025 mmol). <hi rend="subscript"> 2< / hi> O₂ (125 ml) was added, followed by TFA (2.5 ml). The resin was shaken for 4 h at 40 °C. The eluate and an additional volume of TFA (2 ml) for washing were collected and processed using a N₂ <hi rend="subscript"> 2< / hi> The peptide was dried using a hydrofluoric acid stream. Ice-cold diethyl ether (35 ml) was added, and the peptide was precipitated at -20 °C for 2 h. This was followed by centrifugation (7.142 g) for 4 min at 4 °C. The supernatant was removed, and ice-cold diethyl ether (35 ml) was added again, followed by centrifugation (7.142 g) for 4 min at 4 °C. The supernatant was again removed, and the peptide pellet was dried in an oven at 50 °C for 30 min. The linear peptide was dissolved in a 1:1 (vol / vol) mixture of acetonitrile / water (2 ml) and treated with NH₃. <hi rend="subscript"> 4< / hi> HCO <hi rend="subscript"> 3< / hi> (100 mM, 23 ml) was diluted to a final concentration of 1 mM peptide. TCEP (0.025 mmol, 6 mg, 1 eq) was added to this solution. Cyclization was initiated by adding TATA (8 mg, 0.0325 mmol, 1.3 eq) and the mixture was shaken for 1 h at 30 °C. The pH was then adjusted to 2.0 with 10% TFA / water. This solution was then lyophilized and the peptide crude product was purified by RP-HPLC. Comparative example 2: Synthesis of TKR2-08 <p xml:id="_e747390545" n="0055">The synthesis of TKR2-08 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink-amide resin (139 mg, 0.1 mmol, 0.71 mmol / g). In contrast to TKR2-24, Fmoc-L-Met-OH (149 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 4. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µL, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Compound TKR2-08 is a compound corresponding to a compound of general formula I, where D is D1, Y is Y2, except that in this case X is S, m is 1, n is 0 and A is A1. Example 3: Synthesis of TKR2-14 <p xml:id="_e747390549" n="0056">The synthesis of TKR2-14 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-Nle-OH (141 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 4. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 4: Synthesis of TKR2-44 <p xml:id="_e747390553" n="0057">The synthesis of TKR2-44 was carried out according to the procedure for TKR2-24 starting from Fmoc-Rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-selenomethionine-OH (167 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 4. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 5 Synthesis of TKR2-80 <p xml:id="_e747390557" n="0058">The synthesis of TKR2-80 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-Ser(Et)-OH (142 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 4. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 6: Synthesis of TKR2-84 <p xml:id="_e747390561" n="0059">The synthesis of TKR2-84 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, 3-(2-(2-(4-(((2-Bis(2-(tert-butoxy)-2-oxoethyl)amino)cyclohexyl)(2-(tert-butoxy)-2-oxoethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)propanoic acid was used for the N-terminal acylation. This building block was prepared by using di-tert-butyl-2,2'-((2-((2-(tert-butoxy)-2-oxoethyl)(prop-2-yn-1-yl)amino)cyclohexyl)azandiyl)diacetate. <hi rend="superscript"> 16< / hi> (22 mg, 0.045 mmol, 1 eq.) together with N <hi rend="subscript"> 3< / hi> -Peg <hi rend="subscript"> 3< / hi> -OH (11 mg, 0.045 mmol, 1 eq.) was dissolved in DMF (2 ml). CuSO₄ <hi rend="subscript"> 4< / hi> ×5H <hi rend="subscript"> 2< / hi> O₂ (5 mg, 0.02 mmol, 0.5 eq.) and THPTA (12 mg, 0.02 mmol, 0.5 eq.) were dissolved in water (100 µl) and added to the solution. Sodium ascorbate (13 mg, 0.07 mmol, 1.5 eq.) was dissolved in water (100 µl) and added to the solution. The reaction was carried out for 3 hours at room temperature. The solvent was removed under vacuum, and the residue was dissolved in water (3 mL) and extracted with ethyl acetate (3 x 3 mL). The combined organic phase was dried over MgSO₄, and the solvent was removed under vacuum. The residue was used in the next step without further purification. For the N-terminal acylation, 3-(2-(2-(4-(((2-(Bis(2-(tert-butoxy)-2-oxoethyl)amino)cyclohexyl)(2-(tert-butoxy)-2-oxoethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)propanoic acid (14 mg, 0.019 mmol, 1.5 eq., 0.2 M in DMF), DIPEA (0.019 mmol, 7 µl, 4 eq.) and HATU (7 mg, 0.019 mmol, 1.5 eq.) were used., 0.5 M in DMF) to the swollen resin (0.0125 mmol) and the mixture was shaken for 4 hours. Example 7 Synthesis of TKR3-08 <p xml:id="_e747390569" n="0060">The synthesis of TKR3-08 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (35 mg, 0.025 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-O2Oc-OH (39 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for N-terminal acylation. <p xml:id="_e747390570" n="0061">2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(1-(4-(((S)-1-amino-1-oxo-6-(4-(p-tolyl)butanamido)hexan-2-yl)carbamoyl)phenyl)-1H-1,2,3-triazol-4-yl)propanoic acid was synthesized by dissolving Fmoc-Pra-OH (21 mg, 0.064 mmol, 2 eq.) and (S)-N-(1-Amino-1-oxo-6-(4-(p-tolyl)butanamido)hexan-2-yl)-4-azidobenzamide <hi rend="superscript"> 17< / hi> (14 mg, 0.032 mmol, 1 eq.) in DMF (2 mL). CuSO <hi rend="subscript"> 4< / hi> ×5H <hi rend="subscript"> 2< / hi> O₂ (4 mg, 0.016 mmol, 0.5 eq.) and THPTA (8 mg, 0.016 mmol, 0.5 eq.) were dissolved in water (100 µl) and added to the solution. Sodium ascorbate (19 mg, 0.095 mmol, 3 eq.) was dissolved in water (100 µl) and added to the solution. The reaction was carried out for 3 hours at room temperature. The solvent was removed under vacuum, and the residue was purified by RP-HPLC. <p xml:id="_e747390574" n="0062"> For further N-terminal acylation, 2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(1-(4-(((S)-1-amino-1-oxo-6-(4-(p-tolyl)butanamido)hexan-2-yl)carbamoyl)phenyl)-1H-1,2,3-triazol-4-yl)propanoic acid (9 mg, 0.011 mmol, 1.1 eq., 0.2 M in DMF), DIPEA (0.022 mmol, 4 µl, 2.2 eq.) and PyBOP (6 mg, 0.011 mmol, 1.1 eq., 0.5 M in DMF) were added to the swollen resin (0.01 mmol) and the mixture was shaken for 12 h. Example 8 Synthesis of TKR3-18 <p xml:id="_e747390577" n="0063">The synthesis of TKR3-18 was carried out according to the procedure for TKR2-24 starting from Fmoc-Rink amide resin (139 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-Cys(Et)-OH (149 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 4. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 9 Synthesis of TKR3-30 <p xml:id="_e747390581" n="0064">The synthesis of TKR3-30 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (35 mg, 0.025 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-O2Oc-OH (39 mg, 0.1 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for N-terminal acylation. Furthermore, (R)-NODAGA(tBu) was used for the subsequent N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 10: Synthesis of TKR3-34 <p xml:id="_e747390585" n="0065">The synthesis of TKR3-34 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (35 mg, 0.025 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-Peg was used. <hi rend="subscript"> 8< / hi> -OH (65 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as an amino acid building block for N-terminal acylation. Furthermore, (R)-NODAGA(tBu) was used for the subsequent N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 11 Synthesis of TKR3-40 <p xml:id="_e747390590" n="0066">The synthesis of TKR3-40 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (175 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-L-2Nal-OH (142 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used as the amino acid building block for position 2. Furthermore, (R)-NODAGA(tBu) was used for the N-terminal acylation. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 1.5 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. Example 12 Synthesis of TKR3-42 <p xml:id="_e747390594" n="0067">The synthesis of TKR3-42 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (175 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, for the N-terminal acylation, 6-fluoronicotinic acid (5.3 mg, 0.0375 mmol, 1.5 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 13 µl, 3 eq.), and HATU (14 mg, 0.0375 mmol, 1.5 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol), and the reaction mixture was shaken for 2 h. Example 13 Synthesis of TKR3-46 <p xml:id="_e747390597" n="0068">The synthesis of TKR3-46 was carried out according to the procedure for TKR2-24, starting from Fmoc-Rink amide resin (175 mg, 0.1 mmol, 0.72 mmol / g). In contrast to TKR2-24, Fmoc-Sar-OH (125 mg, 0.4 mmol, 4 eq., 0.2 M in DMF) was used ten times and Fmoc-3-aminopropanoic acid (15.6 mg, 0.05 mmol, 2 eq., 0.2 M in DMF) once for the N-terminal acylation. For the further N-terminal acylation, (R)-NODAGA(tBu) was used. <hi rend="subscript"> 3< / hi> (27 mg, 0.05 mmol, 2 eq., 0.2 M in DMF), DIPEA (0.1 mmol, 17 µl, 4 eq.) and HATU (19 mg, 0.05 mmol, 2 eq., 0.5 M in DMF) were added to the pre-swollen resin (0.025 mmol) and the reaction mixture was shaken for 12 h. <p xml:id="_e747390599" n="0069">Table 2 below presents the mass spectrometric data, purity, and yield of the compounds of Examples 1 to 13 according to the invention. <title desc="title"> Table 2< / title> TKR2-14C114H155N27O32S31256.03201256.0310 > 986.0 mg (13%) TKR2-24C113H153N27O33S31257.02161257.0204 > 986.4 mg (10%) TKR2-44C113H153N27O32S3Se1288,98241288,9849 > 612.3 mg (7%) TKR2-80C113H153N27O33S31257,02161257,0223 > 984.7 mg (7%) TKR2-84C122H167N29O36S31356,07181356,0730 > 951.9 mg (6%) TKR3-08C148H199N35O40S31633,6538 c1633,6563 #d> 960.6 mg (6%) TKR3-18C113H153N27O32S41265,01021265,0103 > 975.2 mg (8%) TKR3-30C119H164N28O36S31329,55851329,5584 > 952.1 mg (6%) TKR3-34C131H188N28O42S31461,63711461,6361>991.8mg (5%) TKR3-40C113H153N27O33S31265.01011265.0095 > 975.8 mg (8%) TKR3-42C104H132FN25O27S31039,95081039,9012>982.3mg (3%) TKR3-46C146H208N38O44S31647,72571647,7245 > 952.8 mg (5%) a High-resolution mass spectrometry was performed. b The chemical purity was determined using analytical RP-HPLC and is specified for 230 nm. c m / z calculated for [M+Cu 2+ ] 2+ d m / z found for [M+Cu 2+ ] 2+ Example 14 Fluorescence anisotropy-based competition assay to determine the binding affinities (Kd values) of non-radioactive peptides to recombinant human Nectin-4 All experiments were performed at 37°C for 1200 s (37 s interval) using a Cytation 5 multimode microplate reader (BioTek Instruments, Gen 5 software) and black microtiter plates (BRAND plates with F-bottom (96-well)). Fluorescence intensities were measured at an excitation wavelength of 540 nm and an emission wavelength of 620 nm. Fluorescence anisotropy values ​​(FA values ​​in r) were calculated by the Gen 5 software from the measured parallel (I∥) and perpendicular (I⊥) fluorescence intensities according to Equation I and a G-factor of 0.87. Further data analysis was performed using GraphPad Prism (version 10.4.1, GraphPad Software, San Diego, CA, USA). The test solutions (100 µL) contained an aqueous solution (99 µL) and DMSO (1% v / v, 1 µL). For the competitive binding assay, constant concentrations of the fluorescent ligand TKR2-09 (1 nM, compound TKR2-09 is a compound of general formula I, where D is D1, Y is Y2, XS is, m is 1, n is 0, and A is 6-TAMRA) and of human Nectin-4 (20 nM) were established. The displacement of TKR2-09 from Nectin-4 was measured at 10 different concentrations of the unlabeled peptide (e.g., 0.24–500 nM, prepared by serial 1:1 dilution). Stock solutions of TKR2-09 (2.5 nM) and Nectin-4 (50 nM) were prepared in HEPES buffer (20 mM, 50 mM NaCl, 0.01% Tween20, pH 7.4), and stock solutions of the peptides under investigation were prepared in 5% DMSO / HEPES buffer. The stock solution of the peptide (20 µL) was pipetted to Nectin-4 (40 µL) and TKR2-09 (40 µL), and the measurement was then started.FA values ​​were averaged over 1200 s, and the plot of FA values ​​as a function of peptide concentration was analyzed by non-linear regression based on the model “[inhibitor] vs. response - Variable slope (four parameters)” (implemented in GraphPad Prism). The resulting IC50 values ​​were converted according to the mathematical equation by Nikolovska-Coleska et al.18 (Kdvon TKR2-09 is 0.94 nM). Table 3 below shows the Kd values ​​of the compounds according to the invention in Examples 1 to 13 and additionally of compounds TKR2-03, TKR2-08 and TKR2-52 (corresponding to prior art compound N188). TKR2-030.73 (0.69-0.77) TKR2-080.70 (0.52-0.94) TKR2-08-025.0 (24.2-26.1) TKR2-141.04 (0.88-1.23) TKR2-241.64 (1.50-1.79 TKR2-441.37 (1.21-1.55) TKR2-500.58 (0.50-0.67) TKR2-52 (=N188)149 (132-175) TKR2-8016.4 (14.6-18.8) TKR3-186.01 (4.76-8.64) The data shown are means with estimated confidence intervals (68%) from three separate experiments (performed in duplicate). Compound TKR2-03 is a compound corresponding to a compound of general formula I, where D is D1, Y is Y2, except that in this case X is S, m is 1, n is 0, and A is acetyl. Compound TKR2-08-0 is a compound corresponding to a compound of general formula I, where D is D1, Y is Y2, except that in this case X is SO, m is 1, n is 0, and A is A1. TKR2-52 corresponds to prior art compound N188. Compound TKR2-50 is a compound corresponding to a compound of general formula I, where D is D1, Y is Y2, except that in this case X is S, m is 0, n is 0, and A is A1. It can be seen that the replacement of methionine (contained in TKR2-08, TKR2-50, TKR2-52) with methoxinine (TKR2-24) or norleucine (TKR2-14) is tolerated with respect to binding affinity towards Nectin-4, as at least comparably good binding affinities are achieved. However, the methionine sulfoxide residue (TKR2-08-0) is significantly less well tolerated, which means that the susceptibility of methionine to oxidation subsequently affects its binding behavior towards Nectin-4. Example 15 Cell binding and internalization of 64Cu and 68Ga-labeled compounds HT-1376 cells were cultured in DMEM and HT-5637 cells in RPMI media enriched with 10% FBS and 1% penicillin / streptomycin at 5% CO2 and 37°C. The cells were seeded into 48-well plates four days prior to the experiment (HT-1376: 50,000 cells / well, HT-5637: 30,000 cells / well). DMEM medium was used for both cell types for the binding assay. All cells were washed once with fresh medium prior to the experiment. To determine total binding, the radioligand was diluted to 10 nM in DMEM medium and added to the cells. Non-specific binding of the radioligand was determined in the presence of compound TKR2-03 (1 µM in well). The plates were incubated at 37 °C for 1 h (shaken at 300 rpm). After incubation, the cells were washed twice with cold PBS+ for approximately 5 min.To determine the internalized fraction of bound radioligand, a wash step with cold PBS+ was replaced by treatment with cold glycine buffer (50 mM, pH 2.3) for 5 min. The cells were then lysed with 0.1% SDS in 0.1 M NaOH. The lysates were measured using a gamma counter. The results were normalized against the protein content of the lysates, determined by a NanoDrop spectrophotometer. To obtain the specific binding data, the non-specific binding data were subtracted from the total binding data. Figure 1 shows cell binding and internalization of the 64Cu-labeled compounds TKR2-08, TKR2-14, TKR2-24, TKR2-80, TKR3-08, TKR3-18, TKR3-30, TKR3-34, TKR3-40, and TKR3-46 in Nectin-4-positive (HT-1376) and Nectin-4-negative (5637) cells.Figure 2 shows cell binding and internalization of the 66Ga-labeled compounds TKR2-08, TKR2-24 and TKR2-52 (corresponding to the state-of-the-art compound N188) in Nectin-4-positive (HT-1376) and Nectin-4-negative (5637) cells. Example 16 Saturation binding assay For the saturation binding assay, total and non-specific binding were determined as described above using 10 different radioligand concentrations (0.156–80 nM or 0.321–160 nM) prepared by serial 1:1 dilution. Plots of "total binding" = f(radioligand) were analyzed by non-linear regression using the "one site-total, accounting for ligand depletion" model as implemented in GraphPad Prism, and plots of "non-specific binding" = f(radioligand) were analyzed by linear regression. Figure 3 shows the saturation binding curves for the 64Cu-labeled ligands TKR2-08 (A), TKR2-24 (B), TKR3-08 (C), TKR3-34 (D), and TKR3-46 (E). Total binding is shown in black, non-specific binding (in the presence of excess non-radioactive ligand) in gray, and specific binding as a circle, an upward-pointing triangle, and a downward-pointing triangle, respectively. The data points represent mean values ​​(±SD) from an experiment performed in multiple determinations (5). Table 4 below summarizes the obtained values ​​for Kd and Bmax, including the coefficient of determination (R²). It can be seen that methionine substitution with methoxinine does not impair the binding of the 64Cu-labeled ligands to cells. Kd [nM]4.05 (±0.24)3.0512.94 (+1.09)4.74 (±0.38)8.18 (±0.53) Bmax[fmol / mg]405.75(±7.70)185.151228.78(±42.54)485.44(±6.20)343.85(±4.08) R 20,990,980,9870,9730,986 Figure 4 shows the saturation binding curves for the 68Ga-labeled ligands TKR2-08 (A), TKR2-52 (B), and TKR2-24 (C). Total binding is shown in black, non-specific binding (in the presence of excess non-radioactive ligand) in gray, and specific binding as a circle, an upward-pointing triangle, and a downward-pointing triangle, respectively. The data points represent mean values ​​(±SD) from an experiment performed in multiple determinations (5). Table 5 below summarizes the obtained values ​​for Kd and Bmax, including the coefficient of determination (R²). It can be seen that methionine substitution with methoxinine does not negatively affect the binding of the 68Ga-labeled ligands to cells. TKR2-08TKR2-52TKR2-24 Kd [nM]4.35 (±0.23)51.32 (±6.68)6.57 (±0.30) Bmax [fmol / mg]672.15 (±11.74)399.75 (±30.53)755.12 (±13.06) R 20,9920,9890,994 The TKR2-52 connection corresponds to the state-of-the-art N188 connection. Example 17 Radiolabeling with [64Cu]Cu2+ [64Cu]CuCl2 was synthesized at the Helmholtz-Zentrum Dresden-Rossendorf on the 30 MeV TR-Flex cyclotron (Advanced Cyclotron Systems, Inc., ACSI, Canada) via the 64Ni(p,n)64Cu nuclear reaction. For a typical radiolabeling procedure, the [64Cu]CuCl2 solution was diluted with ammonium acetate buffer (0.1 M, pH 5.6) to obtain a solution with an activity concentration of 1 MBq / ml. A portion (98 µl) of this mixture was then treated with the peptide stock solution (2 µl, 2 mM in DMSO), and the resulting mixture was incubated for 25 min at 60 °C. Quality control of the radiolabeled peptide chelator conjugates was performed by radio-HPLC analysis. Labeling yields were typically ≥ 99%. The radioactively labeled peptides were used without purification. Example 18 Radiolabeling with [68Ga]Ga3+ [68Ga]GaCl3 was eluted with 0.1 M HCl from a 68Ge / 68Ga generator. For a typical radiolabeling procedure, the [68Ga]GaCl3 solution was diluted with sodium acetate buffer (1 M, pH 4.5). A portion of this mixture was then added to the peptide stock solution (2 mM in DMSO), and the mixture was incubated for 10 min at 90 °C. Quality control of the radiolabeled peptide-chelator conjugates was performed by radio-HPLC. Labeling yields were typically ≥ 99%. The radiolabeled peptides were used without further purification. Example 19 Oxidation assay Stability under oxidative conditions was investigated by treating the 64Cu-labeled peptides with hydrogen peroxide. For this purpose, a 0.03% solution of H₂O₂ (2 µL) was added to the radiolabeled peptides (2 nmol, 48 µL) and incubated at room temperature. The peptide conjugates were analyzed by radio-HPLC after 3, 5, and 7 hours. The half-life was determined by calculating the percentage of intact compound, and the resulting time-dependent radioligand degradation curves were analyzed using one-phase decay (implemented in GraphPad Prism). Figure 8 shows the curves obtained for the time-dependent degradation of the 64Cu-marked variants of the compounds according to the invention of examples 2, 3 and 4 as well as the compound TKR2-08. Table 6 below shows the determined half-lives of the 64Cu-labeled variants of the compounds according to the invention from Examples 2, 3 and 4, as well as of compound TKR2-08. TKR2-083.64 TKR2-246.87 TKR2-440.38 TKR2-503.46 It becomes apparent that replacing methionine (TKR2-08, TKR2-50) with methoxinine (TKR2-24) leads to an improvement in oxidative stability. In contrast, replacing it with selenomethionine (TKR2-44) results in increased susceptibility to oxidation. Example 20 PET quantification of 64Cu and 68Ga labeled compounds Once the tumor volume reached 200 mm³, PET experiments were performed with the radioligands. The ligands were radiolabeled as described above at a molar activity of 25 MBq / nmol. The labeling solutions were diluted in 0.9% NaCl, and approximately 9 MBq (≈ 0.46 nmol) was injected intravenously per mouse. To block Nectin-4 binding, 75 nmol of blocking agent (TKR2-03) was injected simultaneously. A 2-hour PET scan was acquired from the time of injection. A CT scan was also performed. For PET image reconstruction, three-dimensional list-mode data were binned using the 400–600 keV energy window and sorted into 36 timeframes (15 × 0 s, 5 × 30 s, 5 × 60 s, 4 × 300 s, 3 × 600 s, 4 × 900 s). The timeframes were then reconstructed using the Tera-Tomo three-dimensional (3D) algorithm with a voxel size of 0.4 mm, applying corrections for random events, dispersion, attenuation, and radionuclide half-life. Figure 5 shows time-dependent SUV curves for the uptake of radioligands in HT-1376 tumors (A) and the time courses of the tumor-to-blood (B), tumor-to-muscle (C), tumor-to-liver (D), and tumor-to-kidney (E) ratios for the 64Cu-labeled compounds TKR2-08, TKR2-14, TKR2-24, TKR3-08, TKR3-34, and TKR3-46 in tumor-bearing mice. The obtained values ​​are summarized in Table 7 below. Significance compared to [64Cu]Cu-TKR2-08 was determined and indicated (*). Table 7 SUVmean1h-2h Tumor0.410 (±0.157)0.462 (±0.057)0.761 (±0.287) *** SUV mean ratio 1-2n Tumor to muscle 4,904 (±1,930) 2,886 (±0,282) 7,396 (±1,288) ** Tumor to heart 2.101 (±0.718) 1.094 (±0.105) 3.601 (±0.893) Tumor to liver 2.071 (±0.733) 0.937 (±0.103) 4.709 (±1.177) *** Tumor to kidney 0.040 (±0.011) 0.015 (±0.003) ** 0.066 (±0.026) *** TKR3-08 TKR3-34 TKR3-46 SUVmean1h-2h Tumor1.984 (±0.186) ***0.754 (±0.148) ***0.789 (±0.202) *** SUV mean ratio 1-2n Tumor to muscle 4,809 (±0.723) 20,829 (47,835) ***15,468 (±1,468) *** Tumor to heart 0.831 (±0.101) 11.168 (±2.030) *** 8.686 (±3.749) *** Tumor to liver 2,050 (±0.255) 13.43 (±3.484) ***12,682 (±3.285) *** Tumor to kidney 0.229 (±0.037) *** 0.066 (±0.005) *** 0.097 (±0.039) *** Figure 6 shows time-dependent SUV curves for the uptake of radioligands in HT-1376 tumors (A) and the time courses of the tumor-to-blood (B), tumor-to-muscle (C), tumor-to-liver (D), and tumor-to-kidney (E) ratios for the 68Ga-labeled compounds TKR2-08, TKR2-52 (=N188), and TKR2-24 in tumor-bearing mice. The obtained values ​​are summarized in Table 8 below. Significance compared to [68Ga]Ga-TKR2-08 was determined and indicated (*). Table 8 TKR2-08TKR2-52TKR2-24 SUVmean1h-2h Tumor0.481 (±0.171)0.347 (±0.073) *0.353 (±0.089) * SUV mean ratio 1h-2h Tumor to muscle 3.153 (±1.541) 2.743 (±0.129) 2.211 (±0.363) Tumor to heart: 1,880 (±0.885) 1,130 (±0.129) 1,227 (±0.263) Tumor to liver 2,462 (±1,176) 1,636 (±0,172) 1,667 (±0,225) Tumor to kidney 0.065 (±0.031) 0.030 (±0.008) *** 0.058 (±0.006) All animal experiments were conducted in accordance with the guidelines of the German Animal Welfare Ordinance and were approved by the local ethics committee. Xenotransplant tumor models of HT-1376 and -5637 cells were generated in NMRI-enhanced nude mice by subcutaneous cell injection in PBS enriched with 50% (v / v) Matrigel. Abbreviations Boctert-Butyloxycarbonyl DIPEA Diisopropylethylamine DMF (Dimethylformamide) DMSO (Dimethyl sulfoxide) Ethyl Fmoc9-Fluorenylmethoxycarbonyl HATU[O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate] Hydrochloric acid (HCl) HEPESN-2-Hydroxyethylpiperazine-N-2-ethanesulfonic acid HOBt1-Hydroxybenzotriazol HPLC High-performance liquid chromatography Mmethyl PET (Positron Emission Tomography) PyBOP(Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate) RP-HPLC (Reversed-Phase High-Performance Liquid Chromatography) SPECTE single-photon emission computed tomography SPPS Solid-phase peptide synthesis SUVmean Standardised intake value TATA2,4,6-triamino-1,3,5-triamine TCEP(Tris(2-carboxyethyl)phosphine) TFA Trifluoroacetic acid THPTATris(3-hydroxypropyltriazolylmethyl)amine literature 1. Maas, M.; Stuhler, V.; Walz, S.; Stenzl, A. and Bedke, J. Enfortumab vedotin - next game-changer in urothelial cancer. Expert Opin. Bio / . 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Shao, F.; Pan, Z.; Long, Y.; Zhu, Z.; Wang, K.; Ji, H.; Zhu, K.; Song, W.; Song, Y.; Song, X.; Gai, Y.; Liu, Q.; Qin, C.; Jiang, D.; Zhu, J. and Lan, X. Nectin-4-targeted immunoSPECT / CT imaging and photothermal therapy of triple-negative breast cancer. J. Nanobiotechno / ogy 2022, 20, 243 . 9. Duan, X.; Xia, L.; Zhang, Z.; Ren, Y.; Pomper, M. G.; Rowe, S. P.; Li, X.; Li, N.; Zhang, N.; Zhu, H.; Yang, Z.; Sheng, X. and Yang, X. First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET / CT imaging of advanced urothelial carcinoma. Clin. Cancer Res. 2023, DOI: 10.1158 / 1078-0432.CCR-23-0609 . 10. Zhang, J.; Duan, X.; Chen, X.; Zhang, Z.; Sun, H.; Shou, J.; Zhao, G.; Wang, J.; Ma, Y.; Yang, Y.; Tian, X.; Shen, Q.; Yu, W.; He, Z.; Fan, Y. and Yang, X.Translational PET imaging of Nectin-4 expression in multiple different cancers with 68Ga-N188. J. Nucl. Med. 2024, 65, 12S-18S . 11. Wan, Q.; Yuan, H.; Cai, P.; Liu, Y.; Yan, T.; Wang, L.; Zhou, Z.; Zhang, W. and Liu, N. 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Claims

Compounds of general formula I where Y or is; X is selected from the group consisting of O, Se and CH2; D1-Naphthyl (D1) or 2-Naphthyl (D2) is; Laus is selected from the group consisting of L2 L3 L1L4 L5L6 L8L7 consists; A is selected from the group consisting of A1A2A3 A4A5A6 A7A8 A9A10 consists; R 1 selected from the group consisting of H, F, Cl, Br, I, -CF 3 , -CH 3 , -OH and -OCH 3 consists; R 2 -OH or -NH 2 is; Z CH or N is; m 0 or 1 is; n 0 or 1 is and p is an integer between 1 and 10. Compound according to claim 1, wherein X = O or CH2. Compound according to claim 1 or claim 2, wherein A is selected from the group consisting of A1, A2, A3, A6 and A9. Compound according to any of the preceding claims, wherein L L2, L3 or is not present. Compound according to one of the preceding claims, wherein m = 1 and D = D1. Compound according to one of the preceding claims, wherein Y = Y2, X = O, A = A1. Compound according to any of the preceding claims, selected from the following: TKR2-14 TKR2-24 TKR2-80 TKR2-84 TKR3-08 TKR3-18 TKR3-30 TKR3-34 TKR3-42 TKR3-46 Compound according to claim 1, wherein if A is A9; F is [18F]F; and if A is A10; I is [123I]I, [124I]I, [125I]I, [131I]I. Complex comprising a compound according to claim 1, wherein A is A1 to A8, and a radioactive metal ion or Al[18F]F2+. Complex according to claim 9, wherein the radioactive metal ion is selected from the group consisting of [61Cu]Cu2+, [64Cu]Cu2+, [67Cu]Cu2+, [67Ga]Ga3+, [68Ga]Ga3+, [177Lu]Lu3+, [149Tb]Tb3+, [155Tb]Tb3+, [152Tb]Tb3+, [161Tb]Tb3+, [225Ac]Ac3+, [226Ac]Ac3+, [132La]La3+, [133La]La3+, [135La]La3+, [111In]In3+, [86Y]Y3+, [90Y]Y3+, [212Bi]Bi3+, [213Bi]Bi3+, [43Sc]Sc3+, [44Sc]Sc3+, [203Pb]Pb3+, [212Pb]Pb3+ consists. Compound according to any one of claims 1 to 8 or complex according to any one of claims 9 or 10 for use as a medicament for the diagnosis and treatment of diseases involving the cell surface protein Nectin-4. Compound or complex according to claim 11, characterized in that the drug is a drug for the diagnosis and treatment of bladder cancer and breast cancer.

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