Development and validation of a panel of cell line derived xenograft models representing multiple tumor indications for the evaluation of targeted radioligand therapeutics

Targeted radioligand therapy (RLT) represents a significant advancement in precision oncology, enabling selective tumor targeting while minimizing damage to healthy tissue. However, the development of innovative RLT agents is often hindered by the limited availability of robust, well-validated preclinical models needed to evaluate target-specific efficacy. Here, we demonstrate the development and validation of a comprehensive panel of in vitro screening assays and in vivo cell line-derived xenografts, including models such as Colo205, MiaPaca2, SHP-77, HT29, A549, LNCaP, and 22Rv1, which express key targets relevant to radioligand therapy. These models provide an ideal pathway for evaluating novel agents in this rapidly growing field, covering targets such as TROP2, CAIX, DLL3, FAP, and PSMA across a range of indications including glioblastoma, colorectal, lung, pancreatic, and prostate cancers. We also discuss the use of in vivo and ex vivo imaging techniques such as single photon emission computed tomography (SPECT) and cryo fluorescence tomography (CFT) . These studies highlight the utility of these platforms for the preclinical development of a wide range of target-based therapies, with potential applications spanning multiple therapeutic modalities including RLT, antibody-drug conjugates (ADCs), and small molecules.