Delayed Imaging Improves Lesion Detectability in [^99mTc]Tc-PSMA-I&S SPECT/CT in Recurrent Prostate Cancer

Our objective was to compare the ability to detect histopathologically confirmed lymph node metastases by early and delayed [^99mTc]Tc-PSMA-I&S SPECT/CT in early biochemically recurrent prostate cancer. Methods: We retrospectively analyzed 222 patients selected for radioguided surgery using [^99mTc]Tc-PSMA-I&S SPECT/CT at different time points after injection (≤4 h and >15 h). In total, 386 prostate-specific membrane antigen (PSMA) PET predetermined lesions were analyzed on SPECT/CT using a 4-point scale, and the results were compared between early and late imaging groups, with uni- and multivariate analyses performed including prostate-specific antigen, injected [^99mTc]Tc-PSMA-I&S activity, Gleason grade group, initial TNM stage, and, stratified by size, PSMA PET/CT-positive lymph nodes. PSMA PET/CT findings served as the standard of reference. Results: [^99mTc]Tc-PSMA-I&S SPECT/CT had a significantly higher positivity rate for detecting lesions in the late than the early imaging group (79%, n = 140/178, vs. 27%, n = 12/44 [P < 0.05] on a patient basis; 60%, n = 195/324, vs. 21%, n = 13/62 [P < 0.05] on a lesion basis). Similar positivity rates were found when lesions were stratified by size. Multivariate analysis found that SUV_max on PSMA PET/CT and the uptake time of [^99mTc]Tc-PSMA-I&S were independent predictors for lesion detectability on SPECT/CT. Conclusion: Late imaging (>15 h after injection) should be preferred when [^99mTc]Tc-PSMA-I&S SPECT/CT is used for lesion detection in early biochemical recurrence of prostate cancer. However, the performance of PSMA SPECT/CT is clearly inferior to that of PSMA PET/CT.