Automated production and bio-evaluation of 11C-DOX for PET imaging histamine H1 receptor

1605 Objectives 11C-Doxepin (11C-DOX)is an established PET probe for imaging the histamine H1 receptor, which is associated with various neurological disorders and allergic diseases. A fully automated cGMP-compliant radiosynthesis is therefore desirable in order to facilitate clinical PET studies. We report here an automated production for 11C-DOX using a multipurpose PET module, and evaluate the tracer using micro-PET imaging. Methods 11C-DOX was radiosynthesized by methylation of nordoxepin using [11C]CH3I in DMF solvent, and then purified by HPLC, and finally reformulated with solid phase extraction using a cGMP-compliant multipurpose PET module developed in house. The final product was analyzed and subjected to quality control according to current USP requirements. Using micro-PET imaging, blocking experiment, and biodistribution studies of 11C-DOX were investigated for imaging the histamine H1 receptor. Results The radiochemical yield (decay corrected) of 11C-DOX for clinical use was 47.0 ± 5.2% (n=12) based on [11C]CH3I, and the radiochemical purity of 11C-DOX was more than 97.5% with 1200 ± 500 Ci/mmol specific activity (EOS). The total production time of 11C-DOX was 37 min from the EOB with the final product passing all tests under cGMP requirements for clinical use. Dynamic micro-PET imaging showed high initial uptake of the tracer, followed by gradual washout. The histamine H1 receptor specificity was subsequently validated through blocking experiments using pretreatment with cold doxepin. Conclusions A simplified and reliable fully automated production of 11C-DOX for clinical use was developed, allowing the synthesis of the tracer with high yield using a cGMP-compliant module and procedure. The synthesized compound demonstrated specific binding to histamine H1 receptor in rat brain using micro-PET imaging