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

Nuclear Medicine and Biology
David ThomaeSteven Staelens

Abstract

Phosphodiesterase 7 (PDE7) hydrolyzes selectively cyclic adenosine monophosphate (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 radiotracer for PDE7 imaging described and detection of PDE7 has only been performed by ex vivo techniques. In this report we describe the radiosynthesis of a novel fluorine-18 labeled radiotracer 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, [(18)F]MICA-003 (PDE7 IC(50)=17 nM) and the corresponding tosylate precursor for radiolabeling. [(18)F]MICA-003 was injected in C57BL/6J mice (n=5) and in vivo images were acquired by μPET imaging. Radiometabolite analysis in plasma and brain was performed to determine the stability of the radioligand. [(18)F]MICA-003 was synthesized by direct fluorination of the tosylate and produced in high decay corrected radiochemical yield (40%), high radiochemical purity (>98%) and high specific activity (86-497 GBq/μmol). μPET imaging revealed that [(18)F]MICA-003 crosses the blood brain barrier and has a homogenous distribution over the brain which washes ...Continue Reading

References

Apr 1, 1990·Trends in Pharmacological Sciences·J A Beavo, D H Reifsnyder
Mar 23, 2005·Bioorganic & Medicinal Chemistry Letters·James KempsonKarl Fischer
Nov 1, 2005·Drug Discovery Today·Miles D HouslayKam Y J Zhang
Jul 18, 2006·Current Pharmaceutical Design·A BloklandJ Prickaerts
Sep 14, 2006·Pharmacological Reviews·Andrew T Bender, Joseph A Beavo
Jun 3, 2008·Seminars in Nuclear Medicine·Karolien GoffinWim Van Paesschen
Oct 13, 2011·Journal of Medicinal Chemistry·Michael S MalamasNicholas J Brandon
Aug 14, 2012·Neuroscience Letters·Emily M JohanssonGuadalupe Mengod
Apr 11, 2013·Expert Opinion on Drug Discovery·Maliheh SafaviMohammad Abdollahi
Sep 16, 2014·ACS Medicinal Chemistry Letters·Peter BuijnstersJosé-Ignacio Andrés

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Citations

May 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Susann SchröderPeter Brust
Feb 11, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Manabu KubotaMakoto Higuchi
Mar 7, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Naoyuki ObokataMakoto Higuchi

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