# Radiosynthesis and Preclinical Evaluation of a Novel 11C‑Labeled Pyrazolopyrimidine Derivative for Positron Emission Tomography Imaging of Phosphodiesterase 2A

## TL;DR

This study develops a new PET radioligand to image PDE2A in the brain, but its in vivo performance needs improvement.

## Contribution

A novel 11C-labeled pyrazolopyrimidine derivative for PDE2A imaging was synthesized and evaluated.

## Key findings

- The radioligand [11C]1 was synthesized with high purity and molar activity.
- In vitro tests showed high accumulation in PDE2A-rich brain regions.
- In vivo PET imaging revealed uniform brain distribution and no significant blocking effects.

## Abstract

Phosphodiesterase
2A (PDE2A) plays a vital role in regulating cyclic
nucleotide signaling by hydrolyzing cAMP and cGMP in the central nervous
system (CNS). This enzymatic activity is essential for neuronal function,
and PDE2A has emerged as a molecular target for neuroimaging in neuropsychiatric
disorders and neurodegenerative diseases. In this study, we evaluated
the novel 11C-labeled positron emission tomography (PET)
radioligand [11C]1 derived from a pyrazolopyrimidine-based
PDE2A inhibitor. The radiosynthesis of [11C]1 was accomplished via [11C]­methyl iodide-mediated methylation
of precursor 9 under mild conditions, yielding [11C]1 with high purity (99%) and high molar activity
(154 ± 66 GBq/μmol). In vitro autoradiography
demonstrated high radiotracer accumulation in regions with abundant
PDE2A expression, including the striatum and substantia nigra. However,
dynamic PET imaging in rats showed a relatively uniform distribution
throughout the brain and no significant blocking effects. Further
optimization in medicinal chemistry is necessary to improve the in vivo performance of the pyrazolopyrimidine-based PDE2A
tracer scaffold.