Abstract 5820: Biodistribution analysis of Leutetium-177 radiopharmaceuticals in mammary, prostate, and glioblastoma models using Alpha-SPECT Mini and gamma counts

Abstract Background: Radiopharmaceuticals play a pivotal role in both diagnostic imaging and targeted radionuclide therapy for cancer. With the increase in clinical use and expansion of oncology indications, accurate characterization of their biodistribution is essential to optimize tumor targeting and reduce systemic toxicity. This study utilizes two approaches, the Alpha-SPECT Mini imaging system and gamma counts, to evaluate the in vivo distribution of radiopharmaceutical agents across three clinically relevant tumor types: human mammary gland adenocarcinoma, prostate carcinoma, and glioblastoma. By utilizing these two methods we aimed to improve profiling of radioligand uptake and clearance patterns across various tumor types and radiopharmaceuticals. Methods: Subcutaneous xenografts of MDA-MB-231 human mammary gland adenocarcinoma, 22Rv1 and LNCaP human prostate carcinoma, and orthotopic xenografts of U-87 MG-Luc2 human glioblastoma in athymic nude mice were treated with lutetium-177 (177Lu) conjugated Anti-human CD44 (10 µCi), 177Lu-Anti-human PSMA (20-22 µCi or 10 µCi), or 177Lu-Anti-human EGFRvIII (10 µCi), respectively, at a mean start size of 300 mm3 (subcutaneous) or 3 weeks post cell implant (orthotopic). Alpha-SPECT Mini imaging was performed at 24, 72 and 168 hours post-dose and tissues for gamma counts were collected at 4, 24, 48, 72, and 168 hours post-dose. Results: Preferential uptake of the radioligand in the tumor was apparent by 24 hours post-dose in the LNCaP, 22Rv1 and U87 MG-Luc2 xenografts, while the MDA-MB-231 xenograft had lower concentrations in comparison to the liver, serum, spleen and whole blood. By 48 hours, only the liver and spleen had higher concentrations than the MDA-MB-231 tumor. Radioligand clearance was observed as early as 48 hours in the MDA-MB-231 tumors. Alpha-SPECT Mini showed similar biodistribution and dynamics of the radioligands to the gamma counts. Conclusions: Alpha-SPECT Mini imaging and gamma counting provided complementary profiling of radiopharmaceutical biodistribution across tumor types. Tumor-specific uptake patterns were evident, differences in radioligand retention, clearance, and off-target accumulation were observed. These findings underscore the importance of tumor biology in radiopharmaceutical pharmacokinetics and highlight the value of multimodal approaches for accurate profiling and therapeutic optimization. Citation Format: Kathryn R. Meshaw, William F. Durham, Karsten E. Fynboe, Tyler Rowe, Jacob C. Hauser, Joseph P. Kolb, Kenneth A. Meshaw, Stephanie M. Fogerson, Beth A. Hollister, . Biodistribution analysis of Leutetium-177 radiopharmaceuticals in mammary, prostate, and glioblastoma models using Alpha-SPECT Mini and gamma counts 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 5820.