Background: Prostate cancer (PC) is the second most frequent malignancy in men globally. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is overexpressed in PC. Recently, several new ⁶⁸Ga- and ¹⁸F-based PSMA-targeted PET agents have been approved by the FDA to detect PC, which offer improved sensitivity and specificity compared to traditional imaging. Methods: PROPELLER (NCT04839367) investigated ⁶⁴Cu-SAR-bisPSMA in 30 men with untreated, histopathologically proven, primary PC with intermediate- to high-risk features. At screening, patients completed ⁶⁸Ga-PSMA-11 PET/CT at 1h post dose. Following enrollment, patients received either 100MBq, 150MBq or 200MBq of ⁶⁴Cu-SAR-bisPSMA, followed by PET/CT at 2-4h post dose. Safety was evaluated before and after ⁶⁴Cu-SAR-bisPSMA dosing. The ⁶⁸Ga-PSMA-11 and ⁶⁴Cu-SAR-bisPSMA PET/CT scans were evaluated by 2 independent, blinded central readers for image quality, PC detection, and intensity of tracer uptake in lesions (SUVmax and Tumor-to-Background Ratio [TBR]). Results: A single, Grade 1 ⁶⁴Cu-SAR-bisPSMA-related AE was reported in the 200MBq cohort. Both readers scored 200MBq of ⁶⁴Cu-SAR-bisPSMA as the dose providing the highest image quality. In this cohort, ⁶⁴Cu-SAR-bisPSMA and ⁶⁸Ga-PSMA-11 was able to detect primary PC in 100% and 77.8% of patients for Reader 1 and 85.7% and 83.3% of patients for Reader 2, respectively. In the 200MBq cohort, Reader 1 identified 41 lesions with ⁶⁴Cu-SAR-bisPSMA vs 36 lesions with ⁶⁸Ga-PSMA-11, while Reader 2 identified 31 lesions with ⁶⁴Cu-SAR-bisPSMA vs 22 lesions with ⁶⁸Ga-PSMA-11. In the 200MBq cohort, ⁶⁴Cu-SAR-bisPSMA consistently showed higher uptake compared to ⁶⁸Ga-PSMA-11 (SUVmax: Reader 1 median [IQR]: 31.40 [27.45] vs 10.08 [13.92], p < 0.001, Reader 2 median [IQR]: 41.00 [46.09] vs 14.58 [14.98], p < 0.001); TBR: Reader 1 median [IQR]: 49.07 [67.69] vs 21.91 [35.71], P = 0.0015), Reader 2 median [IQR]: 76.34 [66.37] vs 23.90 [33.05], p < 0.001). Conclusions: ⁶⁴Cu-SAR-bisPSMA was safe and effective for detecting PSMA-expressing lesions. 200 MBq of ⁶⁴Cu-SAR-bisPSMA was determined as the optimal dose for future trials. ⁶⁴Cu-SAR-bisPSMA PET/CT showed a greater number of lesions and lesions exhibited significantly higher uptake when compared to ⁶⁸Ga-PSMA-11 in men being with intermediate- to high-risk PC. Further studies to evaluate ⁶⁴Cu-SAR-bisPSMA as an imaging agent in patients with biochemical recurrence of PC are underway. Clinical trial information: NCT04839367.