Radiosynthesis of 11C-EACT as a probe for progesterone receptor

1075 Objectives The level of progesterone receptor (PR) in breast cancer can be used to guide the selection of endocrine therapy for the patient. For both diagnosis and therapy of the early breast cancer, a nonsteroidal PR ligand with very high PR binding affinity and low affinity for other steroidal receptors was prepared and radiolabeled with Carbon-11, 5-[4-(2-hydroxy-ethyl)-4-methyl-2-oxo-1,4-dihydro-2H-benzo- [d][1,3]oxazin-6-yl]-1-[11CH3]methyl-1H-pyrrole-2-carbonitrile(11C-EACT). Methods To a solution of the radiolabeled precursor in DMF and solid inorganic base K2CO3, 11CH3I was bubbled under the stream of nitrogen at -20 oC. Then the vessel was heated at 85 oC for 9 min. The crude mixture was separated and purified by a semi-preparative HPLC (H2O:CH3CN= 6:4, 15 mL/min). The final radiotracer was collected in a flask. The solution was then passed through a C-18 cartridge and washed with 1.5 mL of diethyl ether. Finally, the diethyl ether was evaporated and the residue was dissolved with 0.05 mL alcohol and 1.0 mL saline. Identification of the product and radiochemical purity were determined by the reverse-phase HPLC C18 analytical column (H2O:CH3CN= 6:4, 1 mL/min). Results Analytical and semi-preparative HPLC separation protocols were developed for 11C-FPCT and it was isolated in very high purity. 11C-EACT was obtained with an uncorrected radiochemical yield of 16%, a radiochemical purity of 98%, and a high specific activity of 3.3 Ci/μmol. It is stable in vitro within 2 hours. Conclusions The radiosynthesis of 11C-EACT was developed, with favorable in vitro stability. It has potential application for monitoring the PR level by PET imaging. Research Support National Natural Science Foundation of China (21001055), Doctoral Project for Enterprise of Jiangsu province and Key Medical Talent Project of Jiangsu Province (RC2011097).