Matched-Pair Comparison of 68 Ga-PSMA-11 and 18 F-rhPSMA-7 PET/CT in Patients with Primary and Biochemical Recurrence of Prostate Cancer: Frequency of Non-Tumor-Related Uptake and Tumor Positivity

• Published in: Journal of Nuclear Medicine Vol. 62; no. 8; pp. 1082 - 1088
• Main Authors: Kroenke, Markus, Mirzoyan, Lilit, Horn, Thomas, Peeken, Jan C, Wurzer, Alexander, Wester, Hans-Jürgen, Makowski, Marcus, Weber, Wolfgang A, Eiber, Matthias, Rauscher, Isabel
• Format: Journal Article
• Language: English
• Published: United States 01.08.2021
• Subjects: Aged; Aged, 80 and over; Antigens, Surface - metabolism; Biological Transport; Edetic Acid - analogs & derivatives; Fluorine Radioisotopes; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II - metabolism; Humans; Male; Middle Aged; Neoplasm Recurrence, Local - diagnostic imaging; Oligopeptides - chemistry; Oligopeptides - metabolism; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Recurrence; Retrospective Studies; prostate cancer; 68Ga-PSMA-11; radiohybrid PSMA (rhPSMA); 18F-rhPSMA-7; PET; prostate-specific membrane antigen (PSMA)
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.120.251447

Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of prostate cancer theranostic agents. F-rhPSMA-7 offers the advantages of F labeling and low urinary excretion compared with Ga-PSMA-11. Here, we compare the frequency of non-tumor-related uptake and tumor positivity with Ga-PSMA-11 and F-rhPSMA-7 in patients with primary or recurrent prostate cancer. This retrospective matched-pair comparison matched 160 F-rhPSMA-7 with 160 Ga-PSMA-11 PET/CT studies for primary staging ( = 33) and biochemical recurrence ( = 127) according to clinical characteristics. Two nuclear medicine physicians reviewed all scans, first identifying all PET-positive lesions and then differentiating lesions suggestive of prostate cancer from those that were benign, on the basis of known pitfalls and ancillary information from CT. For each region, the SUV of the lesion with the highest PSMA ligand uptake was noted. Tumor positivity rates were determined, and SUV was compared separately for each tracer. F-rhPSMA-7 and Ga-PSMA-11 PET revealed 566 and 289 PSMA ligand-positive lesions, respectively. Of these, 379 and 100 lesions, equaling 67.0% and 34.6%, respectively, of all PSMA-positive lesions, were considered benign. The distribution of their etiology was similar (42%, 24%, and 25% with F-rhPSMA-7 vs. 32%, 24%, and 38% with Ga-PSMA-11 for ganglia, bone, and unspecific lymph nodes, respectively). All primary tumors were positive with both agents ( = 33 each), whereas slightly more metastatic lesions were observed with Ga-PSMA-11 in both disease stages (113 for F-rhPSMA-7 and 124 for Ga-PSMA-11). The SUV of F-rhPSMA-7 and Ga-PSMA-11 did not differ ( > 0.05) in local recurrence or primary prostate cancer; however, the tumor-to-bladder ratio was significantly higher with F-rhPSMA-7 (4.9 ± 5.3 vs. 2.2 ± 3.7, = 0.02, for local recurrence; 9.8 ± 9.7 vs. 2.3 ± 2.6, < 0.001, for primary prostate cancer). The tumor positivity rate was consistently high for Ga-PSMA-11 and F-rhPSMA-7. Both tracers revealed a considerable number of areas of uptake that were reliably identified as benign by trained physicians making use of corresponding morphologic imaging and known PSMA pitfalls. These were more frequent with F-rhPSMA-7. However, the matched-pair comparison could have introduced a source of bias. Adequate reader training can allow physicians to differentiate benign uptake from disease and be able to benefit from the logistical and clinical advantages of F-rhPSMA-7.