Comparison of Posttherapy 4- and 24-Hour [177Lu]Lu-PSMA SPECT/CT and Pretherapy PSMA PET/CT in Assessment of Disease in Men with Metastatic Castration-Resistant Prostate Cancer.

[¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). [¹⁷⁷Lu]Lu-PSMA SPECT/CT 24 h after injection has shown potential as a response biomarker for [¹⁷⁷Lu]Lu-PSMA therapy but is not convenient for patients. This study investigated 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT as an alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for evaluation of treatment response. Methods: This prospective analysis enrolled 23 patients diagnosed with mCRPC commencing [¹⁷⁷Lu]Lu-PSMA-I&T therapy. Two patients were excluded because of incomplete imaging data. Posttherapy SPECT/CT was performed at 4 and 24 h after the first dose and 4 h after the second dose. Baseline [⁶⁸Ga]Ga-PSMA-11 PET/CT and 4- and 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT were analyzed both visually and semiquantitatively. Bland-Altman plots assessed agreement of semiquantitative parameters from the 4- and 24-h scans. Quantitative assessment of the change in the total tumor volume (TTV) on the 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT after the first and second doses was correlated to patient outcomes. Results: All patients had mCRPC previously treated with an androgen receptor pathway inhibitor, and 11 (52%) received prior taxane chemotherapy. Median age was 78 y, and median prostate-specific antigen level was 54 ng/mL. On visual analysis, disease distribution was unchanged among the 3 imaging methods. Eleven patients (52%) had a median of 1 lesion not identified on 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT compared with 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT. All missed lesions on the 4-h [¹⁷⁷Lu]Lu SPECT/CT were smaller than 2 cm. Mean differences and agreement between 4- and 24-h SPECT/CT quantitative parameters were within acceptable bounds for lesion number, SUV_max, and SUV_mean, with higher variation observed for TTV. The change in TTV between dose 1 and 2 [¹⁷⁷Lu]Lu-PSMA SPECT/CT predicted prostate-specific antigen progression-free survival. Conclusion: [¹⁷⁷Lu]Lu-PSMA SPECT/CT at 4 h after injection appears a promising alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for treatment response assessment, with improved patient convenience.