Purpose <p>PSMA PET has been proposed for guiding targeted prostate biopsies. As the rate of clinically significant prostate cancer (csPCa) is positively correlated with PSA density (PSAd), a potential application for PSMA-guided biopsies may be men with negative MRI-first (PI-RADS-1-2) but increased PSAd. The PRIMARY scoring system, using the intraprostatic PSMA-pattern was developed and tested using [⁶⁸Ga]Ga-PSMA-11 and proposed to be universal across PSMA-ligands, however no data on [¹⁸F]PSMA-1007 for biopsy guidance exists. Thus, the aim of this study was to evaluate the PRIMARY score for prostate biopsy guidance using [¹⁸F]PSMA-1007 in a prospective clinical setup.</p> Methods <p>91 patients were prospectively enrolled for [¹⁸F]PSMA-1007 PET/MRI, 86 of these for biopsy guidance after negative MRI or non-csPCa biopsies from PI-RADS 3–5 lesions and persistent suspicion of csPCa. Transperineal MRI/ultrasound fusion target biopsies were performed predominantly from PRIMARY 3–5 lesions. Nine patients with PRIMARY 1–2 did not undergo target biopsies. CsPCa was defined as ISUP grade ≥ 2.</p> Results <p>In a per patient analysis, 23.3% (20/86) were diagnosed with csPCa. In line with previous studies, the rate of csPCa increased with higher PRIMARY score in a per lesion analysis, constituting 0% (0/1), 0% (0/8), 7.2% (7/97), 60% (15/25), and 60% (6/10) for PRIMARY 1, 2, 3, 4, and 5 lesions, respectively. The 7.2% PRIMARY-3 lesions containing csPCa exhibited common characteristics such as anterior location or lack of well-defined separation from the peripheral zone.</p> Conclusion <p>We evaluated the PRIMARY score for use with [¹⁸F]PSMA-1007 and identified benign features and potential “red flags” for PRIMARY-3 lesions. We found csPCa in 23.3% of patients with negative MRI or non-csPCa biopsies from PI-RADS 3–5 lesions and persistent suspicion of csPCa.</p>