Toward Single-Time-Point Image-Based Dosimetry of¹⁷⁷Lu-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 patientspecific 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 177 Lu-PSMA-617 therapy. Methods: 20 mCRPC patients with MTP quantitative 177 Lu-SPECT imaging data (~24h, 48h, 72h post administration) available on first and second 177 Lu-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 (STP H ) and a prior information method (STP prior ) 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 STP H at 48h p.i. for the kidneys had -1.3±5.6% difference against MTP, while STP prior showed a PD of 4.6±6.2%. Smallest average 3 differences for the 56 investigated individual lesions were found using the STP prior approach at 48h p.i. with only 0.4±14.9%, while STP H at 72h p.i. had smallest PD of -1.9±14.8%. Conclusion: STP dosimetry for 177 Lu-PSMA-617 therapy using a single SPECT/CT at 48h or 72h is feasible with a difference of <±20% compared against MTP. Both, STP H and STP prior 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.

Comparison of a 3D CZT and conventional SPECT/CT system for quantitative Lu-177 SPECT imaging

“…An additional 21.2% uncertainty was reported for dosimetry using only single time-point quantitative Lu-177 SPECT imaging at 20 h [ 16 ]. While this study included only ten patients with metastatic hormone-sensitive prostate cancer receiving Lu-177 PRLT, findings were in good accordance with the study by [ 17 ] reporting around 20% uncertainty for twenty patients. As a result, this study still underestimated the uncertainties for absorbed dose estimates.…”

A single-institution experience with 177Lu RPT workflow improvements and qualifying the SPECT/CT imaging for dosimetry

“…Despite MTP’s superior technical merits, the main obstacle to dosimetry in the US is the difficulty in returning patients for imaging after the procedure due to reimbursement issues and patient convenience concerns. Recent developments in dosimetry with single time point (STP) imaging studies provide reasonable accuracy in dosimetry output and convenience for patients and clinicians ( 52 , 53 ). Ha¨nscheid et al.…”

Renal and Multiorgan Safety of177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer in the VISION Dosimetry Substudy

“…Although it may lead to a slight underestimation of the expected cumulative absorbed doses in the kidneys of patients with mCRPC treated with 177 Lu-PSMA-617, the simplified approach is recommended as a reliable and appropriate alternative in patients with poor health status ( 24 ). An alternative approach to simplify dosimetry would be to use a single-time-point method in all cycles ( 48 ). Ultimately, using a single time point in cycle 1 and omitting dosimetry from cycle 2 onward might be the next step toward minimizing complexity, costs, and burden for patients.…”