1. Targeted alpha therapy in a systemic mouse model of prostate cancer - a feasibility study
- Author
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Stuparu, Andreea D, Meyer, Catherine AL, Evans-Axelsson, Susan L, Lückerath, Katharina, Wei, Liu H, Kim, Woosuk, Poddar, Soumya, Mona, Christine E, Dahlbom, Magnus, Girgis, Mark D, Radu, Caius G, Czernin, Johannes, and Slavik, Roger
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Liver Disease ,Urologic Diseases ,Digestive Diseases ,Prostate Cancer ,Prevention ,Cancer ,Good Health and Well Being ,Actinium ,Alpha Particles ,Animals ,Cell Line ,Tumor ,Dipeptides ,Disease Models ,Animal ,Feasibility Studies ,Heterocyclic Compounds ,1-Ring ,Humans ,Male ,Mice ,Prostate-Specific Antigen ,Prostatic Neoplasms ,Castration-Resistant ,Radiopharmaceuticals ,PSMA ,targeted alpha therapy ,prostate cancer ,metastatic mouse model ,actinium ,Oncology and carcinogenesis - Abstract
225Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of 225Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq 225Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. Results: C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p
- Published
- 2020