RT Journal Article SR Electronic T1 Feasibility of single time point image-based dosimetry using prior knowledge: application to 177Lu-PSMA-617 and 177Lu-PSMA-I&T therapy of prostate cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 2554 OP 2554 VO 63 IS supplement 2 A1 Brosch-Lenz, Julia A1 Astrid, Delker A1 Kaiser, Lena A1 Ziegler, Sibylle A1 Bartenstein, Peter A1 Rahmim, Arman A1 Uribe, Carlos A1 Böning, Guido YR 2022 UL http://jnm.snmjournals.org/content/63/supplement_2/2554.abstract AB 2554 Introduction: It has been recognized, that patient-specific absorbed dose estimation plays an important role to allow for personalized radiopharmaceutical therapy (RPT) planning and verification. RPT with Lutetium-177 (177Lu) PSMA ligands has shown promise as an efficient tool in the treatment of metastatic castration-resistant prostate cancer. The knowledge of the radiopharmaceutical effective half-lives (EffT1/2) in organs and tumors is required to perform dosimetry. To estimate patient-specific EffT1/2 patients typically undergo quantitative 177Lu SPECT/CT imaging at multiple time points (MTP) following the radiopharmaceutical injection, which implies additional burden for the patients and might not be feasible in the clinical setting. We aimed to investigate a post-PSMA-therapy dosimetry approach that uses MTP imaging for the 1st treatment cycle and single time point (STP) imaging for the 2nd cycle.Methods: Patients undergoing at least 2 cycles of 177Lu-PSMA-617 (10 patients) and 177Lu-PSMA-I&T (10 patients) therapy were imaged via quantitative 177Lu SPECT at 24h, 48h, and 72h post-injection (p.i.). Volumes of interest (VOIs) for kidneys and whole tumor burden in the field of view were generated by segmenting on the 24h p.i. SPECT images of both cycles using threshold-based approaches in PMOD (v4.005; PMOD Technologies LLC). The EffT1/2 values were obtained by performing a mono-exponential fit on the time-activity-curve (TAC) using the MTP approach for each VOI. The fits were performed for both of the cycles and the time-integrated-activity (TIA) was calculated for the 2nd cycle; considered the true (reference) TIA for the 2nd cycle (TIA2). Next, the EffT1/2 of each VOI from the 1st cycle was used in combination with a STP approach from a single SPECT scan at 24h, 48h or 72h p.i. of the 2nd cycle to estimate the TIA of each VOI. The percentage difference (PD) per VOI between the proposed STP-based TIA and the reference TIA2 was assessed for the 2nd cycle.Results: The MTP-based kidney EffT1/2 values for 177Lu-PSMA-I&T were 25±5h and 27±5h (mean±SD) for 1st and 2nd cycles, respectively, and 31±8h and 30±6h for 177Lu-PSMA-617. For whole tumor burden, EffT1/2 of 48±24h and 44±10h were found for 1st and 2nd cycle of 177Lu-PSMA-I&T. For 177Lu-PSMA-617, the EffT1/2 were 76±30h and 62±18h for whole tumor burden for 1st and 2nd cycles, respectively. Comparing the proposed STP versus reference MTP methods, the PDs in TIA of the 2nd cycle of 177Lu-PSMA-I&T were -4±5%, 0±5%, and 15±27% for the kidneys using the 24h, 48h, or 72h p.i. SPECT, respectively. Similarly, the PDs in TIA for 177Lu-PSMA-617, were 4±9%, -3±7, and 8±15%, for the 24h, 48h, or 72h p.i. SPECT, respectively. For whole tumor burden, the PDs of 177Lu-PSMA-I&T were 7±23%, 4±14%, and 7±12%, and 21±43%, 9±24%, and 11±23% for 177Lu-PSMA-617 using either the 24h, 48h, or 72h p.i. SPECT, respectively.Conclusions: This study assessed the accuracy of STP- versus MTP-based dosimetry approaches for the 2nd therapy cycle using prior knowledge of the effective half-lives from the 1st therapy cycle. For both radiopharmaceuticals and VOIs, the STP approach using the 48h p.i. SPECT had smallest differences against the MTP approach. The maximum PDs (<10%) of the 48h p.i. SPECT-based STP approach were in a clinically acceptable range. We therefore conclude that robust absorbed dose estimates can be obtained for the 2nd cycle using a STP approach to reduce burden for the patients. These results motivate future investigation of STP approaches for subsequent therapy cycles and analysis of more regions and larger patient cohorts.