Continuous, Preclinical Activity Reconstruction in ¹⁷⁷Lu-based Radiopharmaceutical Therapy Using a Sparse Uncollimated γ-Sensor Network.

Abstract

¹⁷⁷Lu-based radiopharmaceutical therapy (RPT) has shown increasing promise in the treatment of neuroendocrine and metastatic prostate cancer. Delivering optimal radiation dose to tumors while minimizing dose to organs-at-risk (OAR) remains an unmet need because of significant patient-to-patient heterogeneity in treatment response, necessitating multiple snapshots of the in vivo activity distribution. Toward this goal, here we present a high temporal resolution activity reconstruction method demonstrated on preclinical prostate cancer models. Using a priori knowledge of tumor locations from a pretherapy scan (eg, positron emission tomography/computed tomography), we have developed a low-cost, sparse sensor network to reconstruct the real-time tumor and OAR activity in preclinical cancer models. The proposed system was successfully validated with: (1) a small custom phantom filled with [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA)-617; and (2) 4 mice models, bearing varying numbers of tumors from 2 human prostate cancer cell lines (PC3-PIP, PC3-flu), to which [¹⁷⁷Lu]Lu-PSMA-617 RPT was administered. Uncollimated γ counts using the developed network were acquired outside of the mouse at 10 minutes post-injection, 6 hours, 12 hours, 24 hours, and 48 hours post-injection. The developed system's total tumor activity and percent injected activity per milliliter of tissue (%IA/mL) reconstruction in tumors, kidneys, and bladders is highly linear with the total tumor activity (R² = 0.991) and %IA/mL (R² = 0.994) from state-of-art small-animal single photon emission computed tomography (SPECT). Acquisition and reconstruction were performed at a 1-minute temporal resolution, >30 times faster than conventional small-animal SPECT imaging, allowing for the ability to capture fast kinetics at early time points and create close-to continuous time-activity curves at a fraction of the cost of small-animal SPECT systems. The system can be used for high temporal resolution preclinical activity reconstruction, and motivates clinical adaptation in order to improve ¹⁷⁷Lu-based RPT quality and safety through frequent activity distribution measurements of multiple tumors and OAR.