PurposeCompared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa).MethodsA retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3–4 h after intravenous injection of 740 MBq99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression.ResultsThe SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0%vs. 47.62%,P= 0.005; 9.09%vs. 88.89%,P= 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with99mTc-HYNIC-PSMA SPECT/CT.Conclusion99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.