Non-specific PSMA-1007 bone uptake evaluated through PSMA-11 PET, bone scan and MRI triple validation in patients with biochemical recurrence of prostate cancer.

Introduction: 18F-PSMA-1007 PET is used in the management of patients with prostate cancer. However, recent reports indicate a high rate of non-specific bone uptake (NSBU) with 18F-PSMA-1007, which may lead to false positive diagnosis. NSBU have not been evaluated thoroughly. Here, we evaluate the frequency of NSBU and bone metastases separately for 18F-PSMA-1007 and 68Ga-PSMA-11 in biochemical recurrence (interindividual comparison). Additionally, we investigate NSBU seen in 18F-PSMA-1007 through follow up examinations (intraindividual comparison) using 68Ga-PSMA-11 PET, bone scintigraphy and MRI. Methods: First, all patients (n = 383) who had 68Ga-PSMA-11 PET between January 2020 and December 2020 and all patients (n = 409) who had 18F-PSMA-1007 PET between January 2020 and November 2021 due to biochemical recurrence were included for an interindividual comparison of bone metastases and NSBU rate. In a second approach, we regarded all patients with NSBU in 18F-PSMA-1007, characterized by focal bone uptake with SUVmax>4 and PSA≤5 ng/ml, who had an additional 68Ga-PSMA-11 PET (n = 17) (interindividual comparison). Of these, 12 patients also had bone scintigraphy and wbMRI within a 1-5-week interval. Bone uptake seen on 18F-PSMA-1007 but not on any of the other four modalities (CT, MRI (n = 1), bone scan and 68Ga-PSMA-11 PET) was recorded as false positive. Results: Patients scanned with 18F-PSMA-1007 PET had a significantly higher rate of NSBU compared with 68Ga-PSMA-11 (140 vs. 64; p<0.001); however, the rate of bone metastases was not significantly different (72 vs. 64; P = 0.7). In the intraindividual comparison group, workup by CT, MRI, bone scan and 68Ga-PSMA-11 PET resulted in a positive predictive value for 18F-PSMA-1007 focal bone uptake (mean SUVmax 6.1±2.9) per patient and per lesion of 8.3 % and 3.6 %, respectively. Conclusion: In patients with PSA≤5 ng/mL and SUV>4 at biochemical recurrence, most 18F-PSMA-1007 focal bone uptake are likely to be false positive and therefore due to NSBU. In case of low clinical likelihood of metastatic disease, 18F-PSMA-1007 bone uptake without morphologic surrogate should be assessed carefully with regard to localization and clinical context. However, the rate of bone metastases was not higher with 18F-PSMA-1007 in the clinical routine, indicating that experienced reporting physicians adjust for NSBU findings.