Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-11C]iomazenil.
The central benzodiazepine receptor tracer [N-methyl-11C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [11C]methyl iodide. The [11C]CH3I (prepared by reduction of [11C]CO2 with LiA1H4 followed by reaction with HI) was reacted with noriomazenil in N,N-dimethylformamide and Bu4N+OH- for 1 min at 80 degrees C and purified by HPLC (C18, 34% CH3CN/H2O 7 mL/min). The product was obtained with synthesis time 35 +/- 5 min (mean +/- SD, n = 7), radiochemical yield (EOB) 36 +/- 16%, radiochemical purity 99 +/- 1%, and specific activity 5100 +/- 2800 mCi/mumol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [11C]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [11C]flumazenil PET and [123I]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [11C]iomazenil will be a useful agent for measuring benzodiazepine receptors in vivo by positron emission tomography.
Baldwin
R M
RM
Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
Horti
A G
AG
Bremner
J D
JD
Stratton
M D
MD
Dannals
R F
RF
Ravert
H T
HT
Zea-Ponce
Y
Y
Ng
C K
CK
Dey
H M
HM
Soufer
R
R
D000328:Adult; D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D010215:Papio; D011963:Receptors, GABA-A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014915:Whole-Body Counting
D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D008024:Ligands; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil