[89Zr]Zr-PSMA-617 PET/CT characterization of indeterminate [68Ga]Ga-PSMA-11 PET/CT findings in patients with biochemical recurrence of prostate cancer: lesion-based analysis.

Background: The state-of-the-art method for imaging men with biochemical recurrence of prostate cancer (BCR) is prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) with tracers containing short-lived radionuclides, e.g., gallium-68 (⁶⁸Ga; half-life: ∼67.7 min). However, such imaging not infrequently yields indeterminate findings, which remain challenging to characterize. PSMA-targeted tracers labeled with zirconium-89 (⁸⁹Zr; half-life: ∼78.41 h) permit later scanning, which may help in classifying the level of suspiciousness for prostate cancer of lesions previously indeterminate on conventional PSMA-targeted PET/CT.

Methods: To assess the ability of [⁸⁹Zr]Zr-PSMA-617 PET/CT to characterize such lesions, we retrospectively analyzed altogether 20 lesions that were indeterminate on prior [⁶⁸Ga]Ga-PSMA-11 PET/CT, in 15 men with BCR (median prostate-specific antigen: 0.70 ng/mL). The primary endpoint was the lesions' classifications, and secondary endpoints included [⁸⁹Zr]Zr-PSMA-617 uptake (maximum standardized uptake value [SUV_max]), and lesion-to-background ratio (tumor-to-liver ratio of the SUV_max [TLR]). [⁸⁹Zr]Zr-PSMA-617 scans were performed 1 h, 24 h, and 48 h post-injection of 123 ± 19 MBq of radiotracer, 35 ± 35 d post-[⁶⁸Ga]Ga-PSMA-11 PET/CT.

Results: Altogether, 6/20 previously-indeterminate lesions (30%) were classified as suspicious (positive) for prostate cancer, 14/20 (70%), as non-suspicious (negative). In these two categories, [⁸⁹Zr]Zr-PSMA-617 uptake and lesional contrast showed distinctly different patterns. In positive lesions, SUV_max and TLR markedly rose from 1 to 48 h, with SUV_max essentially plateauing at high levels, and TLR further steeply increasing, from 24 to 48 h. In negative lesions, uptake, when present, was very low, and decreasing, while contrast was minimal, from 1 to 48 h. No adverse events or clinically-relevant vital signs changes related to [⁸⁹Zr]Zr-PSMA-617 PET/CT were noted during or ~ 4 weeks after the procedure.

Conclusions: In men with BCR, [⁸⁹Zr]Zr-PSMA-617 PET/CT may help characterize as suspicious or non-suspicious for prostate cancer lesions that were previously indeterminate on [⁶⁸Ga]Ga-PSMA-11 PET/CT.

Trial registration: Not applicable.