Abstract
Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein that is highly expressed in 85%-95% of all prostate cancer (PCa) lesions. Histological tissue analyses show a gradually increasing PSMA expression from benign prostate tissue to adenocarcinoma of the prostate. Therefore, PSMA turned into one of the most important PCa cell-surface markers, and is increasingly used for imaging and therapy of PCa.
The first three articles discussed in this work evaluate the performance of $^{68}$Ga-PSMA-11 PET/MRI and $^{68}$Ga-PSMA-11 PET/CT as a re-staging tool in patients with recurrent PCa. We especially focused on the detection rate and distribution of PSMA-positive lesions using $^{68}$Ga-PSMA-11 PET/MRI in patients with low PSA values (≤ 0.5 ng/mL) at the time of scan. In addition, we evaluated the diagnostic yield of $^{68}$Ga-PSMA-11 PET/MRI and $^{68}$Ga-PSMA-11 PET/CT in patients during ongoing androgen deprivation therapy (ADT).
However, a low PSMA surface expression in patients with low-volume or low-grade disease is still a limitation of promising PSMA-based imaging and therapy. Pharmacological induction of PSMA overexpression might be a possibility to improve the detection rate of PSMA-based imaging and to potentially increase the antitumor effect of PSMA-based radioligand therapy. Articles 4-6 of this work describe our attempts to modulate PSMA expression using several approved pharmacological compounds. Dutasteride, a 5α-reductase inhibitor generally used for the treatment of benign prostatic hyperplasia, demonstrated the ability to significantly upregulate PSMA expression and was thus further analyzed in vitro and in vivo. Understanding the regulation of PSMA expression is key to explore further improvements in PCa management.
Kranzbühler, Benedikt Roman Maria