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 11C-
and 18F-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 [11C]harmine
(4.5 ± 0.5) was significantly higher than that for 2-[18F]fluoroethyl-harmol (2.3 ± 0.7) and [11C]clorgyline
(2.0 ± 0.1). A comparable ex vivo biodistribution pattern in
all radiotracers was observed. Furthermore, the tumor uptake of [11C]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 [11C]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.