TY - JOUR T1 - <sup>177</sup>Lu-PSMA-I&amp;T for treatment of metastatic castration resistant prostate cancer: prognostic value of scintigraphic and clinical biomarkers JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.122.264402 SP - jnumed.122.264402 AU - Amir Karimzadeh AU - Matthias Heck AU - Robert Tauber AU - Karina Knorr AU - Bernhard Haller AU - Calogero D'Alessandria AU - Wolfgang Andreas Weber AU - Matthias Eiber AU - Isabel Rauscher Y1 - 2022/09/01 UR - http://jnm.snmjournals.org/content/early/2022/09/22/jnumed.122.264402.abstract N2 - Purpose: The aim of this retrospective analysis was to determine prostate specific antigen (PSA) response, PSA-progression free and overall survival (PSA-PFS and OS) of a large cohort of patients with metastatic castration resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-I&amp;T, and to identify clinical and scintigraphic prognostic factors for outcome. Methods: A total of 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameter as well as findings on post-treatment scintigraphy. Scintigraphic tumor uptake of 177Lu-PSMA-I&amp;T was compared with salivary gland uptake and classified as high and low. The extent of skeletal metastatic disease was estimated by measuring its longest extent and its changes during therapy were used to define scintigraphic progression, response and stable disease. PSA response ≥50%, PSA-PFS and OS were calculated. Results: In total 1138 cycles (median of 3 cycles per patient) of 177Lu-PSMA-I&amp;T using a standard activity of 7.4 GBq were applied intravenously every 4-10 weeks (median 6 weeks). Overall 34% (95% CI, 28%-38%) of patients showed a PSA response ≥50% and median PSA-PFS and OS of the total patient cohort were 16.0 weeks (95% CI, 12.1-19.9) and 13.8 months (95% CI, 12.4-15.5), respectively. Patients with high scintigraphic tumor uptake showed a higher PSA response rate ≥50% (45.7% vs. 10.4%; p&lt;0.0001) and a significantly reduced risk of PSA progression (median event time 24.9 vs. 9.0 weeks, HR 0.3, 95% CI, 0.2-0.5; p&lt;0.0001). In our data risk of death was not significantly different in patients with high scintigraphic uptake compared to low scintigraphic uptake (medians 14.4 vs. 12.4 months, HR 0.9, 95% CI, 0.6-1.3; P = 0.6). In a multivariable analysis the following pretherapeutic prognostic factors for OS were identified: alkaline phosphatase, lactate dehydrogenase, and PSA levels, prior chemotherapy, and the presence of visceral metastases. Scintigraphic response was a strong prognostic factor for PSA response, PSA-PFS, and OS after one treatment cycle. Conclusion: This retrospective analysis of a large group of consecutive patients corroborates previous clinical experience for 177Lu-PSMA-I&amp;T in mCRPC and establishes previously proposed prognostic factors. The skeletal tumor extent and its changes were identified as new potential biomarkers to predict the outcome of therapy after the first treatment cycle. ER -