posted on 2021-08-12, 09:04authored byJustin J. Bailey, Melinda Wuest, Tamara Bojovic, Travis Kronemann, Carmen Wängler, Björn Wängler, Frank Wuest, Ralf Schirrmacher
Phosphodiesterase
5 (PDE5) is a clinically relevant biomarker and
therapeutic target for many human pathologies, yet a noninvasive agent
for the assessment of PDE5 expression has yet to be realized. Such
agents would improve our understanding of the nitric oxide (NO)/cyclic
guanosine 3′,5′-monophosphate (cGMP)/PDE5 pathway in
human pathologies and potentially lead to novel uses of PDE5 inhibitors
to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory
responses. In this study, efforts were made to produce an 18F-labeled analogue of the PDE5 inhibitor tadalafil to visualize PDE5
expression in vivo with positron emission tomography
(PET). However, during the late-stage fluorination step, quantitative
epimerization of the tadalafil C12a stereocenter
occurred, yielding a less active epi-isomer. In vivo dynamic microPET images in mice revealed that the epimerized radiotracer,
[18F]epi-18, rapidly accumulated in the liver
with negligible uptake in tissues of known PDE5 expression.