[Radiosynthesis of peripheral benzodiazepine receptor radioligand [N-methyl-(11)C]PK 11195 as an imaging agent for positron emission tomography].
OBJECTIVE
To establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.


METHODS
(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.


RESULTS
(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.


CONCLUSIONS
The (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.
Wang
Ming-fang
MF
China Institute of Atomic Energy, Beijing 102413, China. mfwang@china.com
Tang
Guang-hua
GH
Li
Bao-yuan
BY
Liang
Ming-quan
MQ
Luo
Zhi-fu
ZF
D000818:Animals; D002250:Carbon Radioisotopes; D003287:Contrast Media / Q000138:chemical synthesis*; D007546:Isoquinolines / Q000009:adverse effects / Q000138:chemical synthesis*; D051379:Mice; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000138:chemical synthesis; D011963:Receptors, GABA-A / Q000378:metabolism*
D002250:Carbon Radioisotopes; D003287:Contrast Media; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C037850:PK 11195