RT Journal Article
SR Electronic
T1 In vivo quantification of [18F]FE-M100907, a potential serotonin 2A receptor PET ligand
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1775
OP 1775
VO 51
IS supplement 2
A1 Jaya Prabhakaran
A1 Vattoly Majo
A1 Matthew Milak
A1 Lydumilla Savenkova
A1 Ramin Parsey
A1 J. John Mann
A1 JS Dileep Kumar
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1775.abstract
AB 1775 Objectives 5-HT2AR are implicated in the complex pathophysiology of neuropsychiatric disorders and also have been proposed as putative targets for antipsychotic drugs. The utility of radiotracers that have been developed so far for in vivo imaging of 5-HT2AR are limited due to their high non specific binding, inadequate pharmacological selectivity, long equilibrium time, and interference of BBB penetrable metabolites. The present study evaluates the quantification of (R)[18F]FE-M100907 (previously reported as ((R)[18F]MHMZ), in non human primates. Methods Methods: Chiral desfluoroethyl-FEM100907 and FE-M100907 were synthesized from (R) 3-(hydroxy(piperidin-4-yl)methyl)-2-methoxyphenol. Radiosyntheses were performed using F-18 produced from RDS112 cyclotron. [18F]FE-M100907 was purified using semipreparative HPLC followed by solid phase extraction. PET scans were performed in adult male Papio Anubis with an ECAT EXACT HR+ scanner after an i.v. bolus injection of 2.1 ± 0.4 mCi of [18F]FE-M100907. Protein binding and metabolite analyses were performed using ultracentrifugation and HPLC analyses. Blocking studies were performed using ketanserin (1 mg/ kg/ i.v.). Results Radiosynthesis of (R)[18F]FE-M100907 has been achieved in 2 steps with an overall yield of 40% at EOS and specific activity 1.5 +/-0.5 Ci/μmmol with >99% chemical and radiochemical purities. PET studies in anesthetized baboon showed a high uptake in brain and distribution of radioactivity was identical to 5-HT2A receptor enriched region whereas cerebellum showed minimal uptake. A fast metabolism was observed with the % of unreacted (R)[18F]FE-M100907 reaching 16% in 30 min, 8% in 60 and 4% in 120 minutes. The free fraction of (R)[18F]FE-M100907 in baboon plasma was ~40%. Conclusions (R)[18F]FE-M100907 is a selective radioligand for in vivo quantification in non human primates. (R)[18F]FE-M100907 has the potential to quantify 5-HT2AR in human