Synthesis and preclinical evaluation of an super(18)F labeled PDE7 inhibitor for PET neuroimaging

• Published in: Nuclear medicine and biology Vol. 42; no. 12; pp. 975 - 981
• Main Authors: Thomae, David, Servaes, Stijn, Vazquez, Naiara, wyffels, Leonie, Dedeurwaerdere, Stefanie, Van der Veken, Pieter, Joossens, Jurgen, Augustyns, Koen, Stroobants, Sigrid, Staelens, Steven
• Format: Journal Article
• Language: English
• Published: 01-12-2015
• ISSN: 0969-8051
• DOI: 10.1016/j.nucmedbio.2015.07.007

Phosphodiesterase 7 (PDE7) hydrolyzes selectively cyclic adenosine mono-phosphate (cAMP) which is an intracellular second messenger. PDE7 is expressed by 2 genes which are both present in the brain. To date there is no radio-tracer for PDE7 imaging described and detection of PDE7 has only been performed by ex vivo techniques. In this report we describe the radio-synthesis of a novel fluorine-18 labeled radio-tracer for PDE7 as well as the in vivo evaluation in mice to verify whether it has potential for imaging of PDE7 in the brain. We have synthesized a potent fluorinated PDE7 inhibitor, [[sup 18]F]MICA-003 and the corresponding tosylate precursor for radio-labeling. Radio-metabolite analysis in plasma and brain was performed to determine the stability of the radio-ligand. We have described the synthesis and in vivo evaluation of a novel radio-ligand far PDE7 imaging. Despite high uptake in the brain and favorable kinetics in vivo, the presence of a brain penetrant radio-metabolite makes [[sup 18]F]MICA-003 unfavorable for the accurate quantification of PDE7 and more stable spiroquinazolinones analogs are in development.