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

Radiopharmaceutical therapies (RPTs) with ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) ligands have demonstrated promising results for the treatment of metastatic castration-resistant prostate cancer. The lack of absorbed-dose-effect relationships currently prevents patient-specific activity personalization. To ease the implementation of dosimetry in the routine clinical workflow for RPT, simplified methods such as single-time-point (STP) instead of multiple-time-point (MTP) imaging protocols are required. This work aimed at assessing differences in the time-integrated activity (TIA) of STP versus MTP image-based dosimetry for ¹⁷⁷Lu-PSMA-617 therapy. Methods: Twenty metastatic castration-resistant prostate cancer patients with MTP quantitative ¹⁷⁷Lu-SPECT imaging data (∼24, 48, and 72 h post injection (p.i.)) 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 a 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 (PDs) in TIA between STP and MTP were compared for the second therapy cycle. Results: Using STP_H at 48 h p.i. for kidneys showed a -1.3% ± 5.6% PD from MTP, whereas STP_prior showed a PD of 4.6% ± 6.2%. The smallest average PDs for the 56 investigated individual lesions were found using STP_prior at 48 h p.i., at only 0.4% ± 14.9%, whereas STP_H at 72 h p.i. had a smallest PD of -1.9% ± 14.8%. Conclusion: STP dosimetry for ¹⁷⁷Lu-PSMA-617 therapy using a single SPECT/CT scan at 48 or 72 h p.i. is feasible, with a PD of less than ±20% compared with MTP. The validity of both STP_H and STP_prior has been demonstrated. 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-effect relationships based on fixed therapy activities that may, in future, allow for absorbed-dose-based RPT activity personalization.