Abstract Targeted radioligand therapy (RLT) has emerged as a promising strategy for precision oncology, enabling selective tumor targeting while reducing collateral damage to healthy tissue. A major challenge in advancing novel RLT agents, however, is the limited availability of well-validated preclinical models for assessing target-specific efficacy. Fibroblast Activation Protein (FAP), a membrane-bound protein with minimal expression in normal tissues but high prevalence in cancer-associated fibroblasts and glioblastoma (GBM) cells, represents an attractive therapeutic target. FAP-2286, a FAP-binding peptide radiolabeled with lutetium-177 (177Lu), offers potential as both an imaging and therapeutic agent. In this study, we evaluate target expression and compare the anti-tumor efficacy of 177Lu-FAP-2286 across multiple immunocompromised mouse models bearing subcutaneous, cell line-derived tumors. Our findings underscore the critical role of model selection in preclinical development and highlight its importance for rational decision-making in RLT programs. Citation Format: Michael Batey, James Suchy, Taylor Hotz, Michael Milhollen, Kayla Duval, Jackson Chan, Karen Gelinas, Michael Bruce, Michelle Petrozzi, William Maccuaig, Neil Rollins, Jennifer Tavares, Erin Snay, Kyeara Mack-Henry, Soumya Ullas, . Validation of a panel of fibroblast activation protein expressing cell line derived xenograft models as a platform for the development of targeted radioligand therapeutics abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4646.
Batey et al. (2026) studied this question.