Consecutive PSMA and AR PET imaging shows positive correlation to AR and PSMA protein expression in primary hormone naïve prostate cancer.

Rationale: The present study set out to investigate if PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of two PET tracers and the corresponding target structures was assessed. The first tracer was [68 Ga]Ga-PSMAHBED-CC([68 Ga]PSMA), which is already implemented in clinical routine. The second tracer was [18 F]-fluoro-5α-dihydrotestosterone([18 F]FDHT) which binds to the androgen receptor (AR). The AR is particularly interesting in PC, since the AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient received a [68 Ga]PSMA-PET/MRI- and [18 F]FDHT-PET/MRI-scan prior to prostatectomy. Cancer standardized uptake values (SUV) were determined and related to background SUVs. Following prostatectomy, tumor tissue was sampled and AR and prostate-specific membrane antigen (PSMA) expression determined. AR and PSMA expressions were evaluated quantitively with QuPath and additionally with a four-tiered rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [18 F]FDHT, the SUVmax /SUVbackground ratio showed a significant, strong correlation (P-value=0.019, r=0.72) with AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [68 Ga]PSMA SUVmax /SUVbackground ratio was not significant (P-value=0.061), yet a positive correlation trend could be observed (r=0.61). SUVmax /SUVbackground ratios were higher for [68 Ga]PSMA (34.9±24.8) compared to [18 F]FDHT (4.8±1.2). In line with this findings, the tumor detection rate of the Ga-PSMA-PET scan was 90%, but only 40% for the [18 F]FDHT-PET scan. The four-tiered rating of PSMA staining intensity yielded very homogenous results with values of 3+ for most subjects (90%). The AR staining was rated with 1+ in two patients (20%), with 2+ in four patients (40%) and with 3+ in four patients (40%). Conclusion: [18 F]FDHT-PET may be useful for monitoring AR expression and alterations of AR expression during treatment of PC patients. This may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [18 F]FDHT-PET is inferior to [68 Ga]PSMA-PET for primary PC diagnosis, but the correlation between [68 Ga]PSMA SUVs and PSMA expression is weaker compared to [18 F]FDHT and the AR.