An ⁸⁹Zr-Labeled PSMA Tracer for PET/CT Imaging of Prostate Cancer Patients

Abstract

The short half-life of existing prostate-specific membrane antigen (PSMA) tracers limits their time for internalization into tumor cells after injection, which is an essential prerequisite for robust detection of tumor lesions with low PSMA expression on PET/CT scans. Because of its longer half-life, the ⁸⁹Zr-labeled ligand ⁸⁹Zr-PSMA-DFO allows acquisition of PET scans up to 6 d after injection, thereby overcoming the above limitation. We investigated whether ⁸⁹Zr-PSMA-DFO allowed more sensitive detection of weak PSMA-positive prostate cancer lesions. Methods: We selected 14 prostate cancer patients with biochemical recurrence who exhibited no PSMA-positive lesions on a PET scan acquired with existing PSMA tracers (⁶⁸Ga-PSMA-11, ¹⁸F-JK-PSMA-7). Within 5 wk after the negative scan result, we obtained a second PSMA PET scan using ⁸⁹Zr-PSMA-DFO (117 ± 16 MBq, PET acquisition within 6 d of injection). Results: ⁸⁹Zr-PSMA-DFO detected 15 PSMA-positive lesions in 8 of 14 patients, who had a PET-negative reading of their initial PET scans with existing tracers. In these 8 patients, the new scans revealed localized recurrence of disease (3/8), metastases in lymph nodes (3/8), or lesions at distant sites (2/8). On the basis of these results, patients received lesion-targeted radiotherapies (5/8), androgen deprivation therapies (2/8), or no therapy (1/8). The plausibility of 14 of 15 lesions was supported by histology, clinical follow-up after radiotherapy, or subsequent imaging. Furthermore, comparison of the 15 ⁸⁹Zr-PSMA-DFO–positive lesions with their correlates on the original PET scan revealed that established tracers exhibited mild accumulation in 7 of 15 lesions; however, contrast-to-noise ratios were too low for robust detection of these lesions (contrast-to-noise ratios, 2.4 ± 3.7 for established tracers vs. 10.2 ± 8.5 for ⁸⁹Zr-PSMA-DFO, P = 0.0014). The SUV_max of the 15 ⁸⁹Zr-PSMA-DFO–positive lesions (11.5 ± 5.8) was significantly higher than the SUV_max on the original PET scans (4.7 ± 2.8, P = 0.0001). Kidneys were the most exposed organ, with doses of 3.3 ± 0.7 mGy/MBq. The effective dose was 0.15 ± 0.04 mSv/MBq. Conclusion: In patients with weak PSMA expression, a longer period of time might be needed for ligand internalization than that offered by existing PSMA tracers to make lesions visible on PET/CT scans. Hence, ⁸⁹Zr-PSMA-DFO might be of significant benefit to patients in whom the search for weak PSMA-positive lesions is challenging. Radiation exposure should be weighed against the potential benefit of metastasis-directed therapy or salvage radiotherapy, which we initiated in 36% (5/14) of our patients based on their ⁸⁹Zr-PSMA-DFO PET scans.