Detection efficacy of [⁸⁹Zr]Zr-PSMA-617 PET/CT in [⁶⁸Ga]Ga-PSMA-11 PET/CT-negative biochemical recurrence of prostate cancer

Rationale: In patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specific membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (⁸⁹Zr; half-life ~ 78.41 h), which allow imaging ≥ 24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides.

Materials and methods: To confirm [⁸⁹Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efficacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [⁸⁹Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual findings and PET variables reflecting lesional [⁸⁹Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum-maximum) prostate-specific antigen (PSA) 0.54 (0.11-2.50) ng/mL, and negative [⁶⁸Ga]Ga-PSMA-11 scans 40 ± 28 d earlier. Primary endpoints were percentages of patients with, and classifications of, suspicious lesions.

Results: Altogether, 18/23 patients (78%) had 36 suspicious lesions (minimum-maximum per patient: 1-4) on both 24-h and 48-h scans (n = 33 lesions) or only 48-h scans (n = 3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confirmed as a nodal metastasis. In all 15 patients given radiotherapy based on [⁸⁹Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h.

Conclusions: In men with BCR and low PSA, [⁸⁹Zr]Zr-PSMA-617 PET/CT seems effective in finding prostate malignancy not seen on [⁶⁸Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [⁸⁹Zr]Zr-PSMA-617 PET/CT is warranted.