Towards Single Time Point Image-Based Dosimetry of ¹⁷⁷Lu-PSMA-617 Therapy

Abstract

Radiopharmaceutical therapies (RPTs) with Lutetium-177 prostate-specific membrane antigen (PSMA) ligands have demonstrated promising results for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The lack of absorbed dose and effect relationships currently prevents from patient-specific activity personalization. To ease the implementation of dosimetry in routine clinic workflow of RPT, simplified methods such as single time point (STP) instead of multiple time point (MTP) imaging protocols are required. This work aims at assessing differences in time-integrated activity (TIA) of STP versus MTP image-based dosimetry for ¹⁷⁷Lu-PSMA-617 therapy. Methods: 20 mCRPC patients with MTP quantitative ¹⁷⁷Lu-SPECT imaging data (~24h, 48h, 72h post administration) available on first and second ¹⁷⁷Lu-PSMA-617 therapy cycles were included in this study. Time-activity-curves were fitted for kidneys and lesions to derive effective half-lives and yield reference TIA. STP approaches involved the formula by Hänscheid (STPH) and a prior information method (STPprior) that uses the effective half-lives from the first therapy cycle. All time points were considered for the STP approaches. Percentage differences (PD) in TIA between STP and MTP was compared for the second therapy cycle. Results: Using STPH at 48h p.i. for the kidneys had -1.3±5.6% difference against MTP, while STPprior showed a PD of 4.6±6.2%. Smallest average differences for the 56 investigated individual lesions were found using the STPprior approach at 48h p.i. with only 0.4±14.9%, while STPH at 72h p.i. had smallest PD of -1.9±14.8%. Conclusion: STP dosimetry for ¹⁷⁷Lu-PSMA-617 therapy using a single SPECT/CT at 48h or 72h is feasible with a difference of <±20% compared against MTP. Both, STPH and STPprior have demonstrated their validity. We believe this finding can increase the adoption of dosimetry and facilitate implementation in routine clinical RPT workflows. Doing so will ultimately enable the finding of dose-effective relationships based on fixed therapy activities that could in future allow for absorbed dose based RPT activity personalization.