This title appears in the Scientific Report : 2022 
An 89Zr-Labeled PSMA Tracer for PET/CT Imaging of Prostate Cancer Patients
Dietlein, Felix
Kobe, Carsten / Vázquez, Sergio Muñoz / Fischer, Thomas / Endepols, Heike / Hohberg, Melanie / Reifegerst, Manuel / Neumaier, Bernd / Schomäcker, Klaus / Drzezga, Alexander E. / Dietlein, Markus (Corresponding author)
Molekulare Organisation des Gehirns; INM-2
Nuklearchemie; INM-5
Journal of nuclear medicine, 63 (2022) 4, S. 573 - 583
New York, NY Soc. 2022
10.2967/jnumed.121.262290
Journal Article
Neuroimaging
OpenAccess
Please use the identifier: http://dx.doi.org/10.2967/jnumed.121.262290 in citations.
Please use the identifier: http://hdl.handle.net/2128/32636 in citations.


The short half-life of existing prostate-specificmembraneantigen (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 6 16 MBq, PET acquisition within 6 d of injection). Results: 89Zr-PSMADFO 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 lesiontargeted 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 6 3.7 for established tracers vs. 10.2 6 8.5 for89Zr-PSMA-DFO, P 5 0.0014). The SUVmax of the 15 89ZrPSMA-DFO–positive lesions (11.5 6 5.8) was significantly higher than the SUVmax on the original PET scans (4.7 6 2.8, P5 0.0001). Kidneys were the most exposed organ, with doses of 3.3 6 0.7 mGy/MBq. The effective dose was 0.15 6 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, 89ZrPSMA-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 benefitof metastasis-directed therapy or salvage radiotherapy, which weinitiated in 36% (5/14) of our patients based on their 89Zr-PSMA-DFO PET scans.