R. Lall1, K. N. Bobba2, A. Bidkar2, Y. Seo2, R. Flavell2, A. Niknejad1, and M. Anwar2; 1University of California, Berkeley, Berkeley, CA, 2University of California, San Francisco, San Francisco, CA
Purpose/Objective(s): 225Ac-based targeted alpha therapy (TAT) has shown promise in the treatment of solid tumors including neuroendocrine and metastatic prostate cancers. Due to the variance in biokinetics, total integrated dose delivered, and dose rate, a system capable of monitoring 225Ac-based TAT biodistribution over time is necessary to ensure sufficient dose to tumors and a safe level of uptake by organs at risk (OAR). Due to the low administered activity in TAT, current SPECT systems have significant shortcomings in reliably tracking TAT biodistribution in vivo, hindering the development of TAT radiopharmaceuticals and their clinical adoption. Utilizing a priori knowledge of tumor and OAR locations from pretherapy imaging (PET/CT or CT), we have developed a novel reconstruction algorithm that uses ? counts from a sparse network of uncollimated, optical fiber scintillation detectors. Here, we present our preliminary preclinical in vivo dose reconstruction results with 225Ac-MACROPA-PEG4-YS5 in a 22Rv1 prostate xenograft.Materials/
Methods: The proposed reconstruction system was validated in an athymic nude mouse bearing a subcutaneous 22Rv1 tumor and intravenously administered 500 nCi of 225Ac-MACROPA-PEG4-YS5. The mouse was placed in a 3D printed scaffold for imaging reliability, and eight uncollimated optical fiber scintillation counters were secured in the scaffold to record ? counts outside the mouse for 2 hours at 4 days post injection (d.p.i). A CT with contrast was used to annotate sensor positions and volumes of the tumor, liver, kidneys, spleen, and heart. This a priori information was used to reconstruct both the total organ activity and percent injected activity per mL of tissue (%IA/mL). Ex vivo biodistribution was performed as a standard-of-comparison. Results: The developed system’s reconstruction of both activity and %IA/mL in the tumor and OARs highly correlates with the activity and %IA/g from ex vivo biodistribution with a Pearson’s r of 0.95 and 0.96, respectively. The absolute errors in the reconstructed activity between the proposed reconstruction method and ex vivo biodistribution for the 22Rv1 tumor, liver, kidney, spleen, and heart are 0.84 nCi, 4.6 nCi, 4.4 nCi, 6.08 nCi, and 0.40 nCi, respectively. The absolute errors between the %IA/mL of the proposed reconstruction method and the %IA/g from the ex vivo biodistribution for the 22Rv1 tumor, liver, kidney, spleen, and heart are 0.05%, 0.89%, 4.11%, 5.26%, and 0.41%, respectively. Conclusion: We have demonstrated a novel in vivo dose reconstruction method in 225Ac-based TAT by utilizing a sparse network of custom ? counters along with a priori knowledge of tumor and OAR locations. The system was validated in aprostate cancer murine model and shown to be highly correlative with ex vivo biodistribution. We envision that the proposed system will enable optimization of new TAT developments and aid their movement towards clinical implementation.
