Utility of ⁶⁴Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on ⁶⁸Ga-PSMA-11 PET/CT

Abstract

Despite a high detection rate of ⁶⁸Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative ⁶⁸Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog ⁶⁴Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of ⁶⁴Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal ⁶⁸Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal ⁶⁸Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. ⁶⁴Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of ⁶⁴Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4–11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28–2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). ⁶⁴Cu-SAR-BBN PET–avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16–0.82). Patients were followed up for a median of 10 mo (IQR, 9–12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: ⁶⁴Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal ⁶⁸Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.