AI Article Synopsis
- Phosphodiesterase 10A (PDE10A) is an important enzyme for brain signaling and neurotransmission, and imaging it via PET could enhance understanding of brain functions and disorders.
- The study focused on developing a new 18F-labeled ligand ([18F]IV) based on a specific chemical structure, resulting in a compound with good purity and specific activity.
- Despite showing metabolic stability and moderate affinity in initial tests, the ligand did not demonstrate target-specific accumulation for effective imaging of PDE10A, making it unsuitable for PET applications.
Article Abstract
Phosphodiesterase 10A (PDE10A) is a key enzyme of intracellular signal transduction which is involved in the regulation of neurotransmission. The molecular imaging of PDE10A by PET is expected to allow a better understanding of physiological and pathological processes related to PDE10A expression and function in the brain. The aim of this study was to develop a new 18F-labeled PDE10A ligand based on a 6,7-dimethoxy-4-pyrrolidinylquinazoline and to evaluate its properties in biodistribution studies. Nucleophilic substitution of the 7-tosyloxy-analogue led to the 7-[18F]fluoroethoxy-derivative [18F]IV with radiochemical yields of 25% ± 9% (n = 9), high radiochemical purity of ≥99% and specific activities of 110-1,100 GBq/μmol. [18F]IV showed moderate PDE10A affinity (KD,PDE10A = 14 nM) and high metabolic stability in the brain of female CD-1 mice, wherein the radioligand entered rapidly with a peak uptake of 2.3% ID/g in striatum at 5 min p.i. However, ex vivo autoradiographic and in vivo blocking studies revealed no target specific accumulation and demonstrated [18F]IV to be inapplicable for imaging PDE10A with PET.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763632 | PMC |
| http://dx.doi.org/10.3390/ph5020169 | DOI Listing |
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