Molecular Imaging of Monoamine Oxidase A Expression in Highly Aggressive Prostate Cancer: Synthesis and Preclinical Evaluation of Positron Emission Tomography Tracers

The role of monoamine oxidase A (MAO-A) in the aggressiveness of prostate cancer (PCa) has been established in recent years. The molecular imaging of MAO-A expression could offer a noninvasive tool for the visualization and quantification of highly aggressive PCa. This study reports the synthesis and preclinical evaluation of C-11- and F-18-labeled MAO-A inhibitors as positron emission tomography (PET) tracers for proof-of-concept studies in animal models of PCa. Good manufacturing practice production and quality control of these radiotracers using an automated platform was achieved. PET imaging was performed in an LNCaP tumor model with high MAO-A expression. The tumor-to-muscle (T/M) uptake ratio of [C-11]harmine (4.5 +/- 0.5) was significantly higher than that for 2-[F-18]fluoroethyl-harmol (2.3 +/- 0.7) and [C-11]clorgyline (2.0 +/- 0.1). A comparable ex vivo biodistribution pattern in all radiotracers was observed. Furthermore, the tumor uptake of [C-11]harmine showed a dramatic reduction (T/M = 1) in a PC3 tumor model with limited MAO-A expression, and radioactivity uptake in LNCaP tumors was blocked in the presence of nonradioactive harmine. Our findings suggest that [C-11]harmine may serve as an attractive PET probe for the visualization of MAO-A expression in highly aggressive PCa. These radiotracers have the potential for clinical translation and may aid in the development of personalized therapeutic strategies for PCa patients.