Abstract:
Imaging of dopamine D
4 receptor with specific radioligand has been of increasing interest in recent years. Herein, a putative dopamine D
4 receptor tracer, 3-(4-
18Ffluorobenzyl)-8, 9-dimethoxy-1, 2, 3, 4-tetrahydrochromeno3, 4-
c pyridin-5-one (
18F-FDTP) was reportedly prepared from
18F
- through a two-step one-pot method. Fluorine-18 was introduced to trimethylammoniumbenzaldehyde triflate by a nucleophilic halogen displacement on it. The fluorine-18 labeled intermediate was then reductively aminated with 8, 9-dimethoxy-1, 2, 3, 4-tetrahydrochromeno3, 4-
c pyridine-5-one to form the target molecule. The radiochemical synthesis of
18F-FDTP take about 105 min with a total radiochemical yield of 19.8% (decaycorrected). Its radiochemical purity is greater than 97% after purification
via HPLC and its specific activity is greater than 6.3×10
4 PBq/mol. Through
in vitroreceptor binding assay, the
Ki of FDTP for D
4.2 receptor is determined to be 8.1 nmol/L, and for D
3, D
2 to be greater than 3 000, 5 800 nmol/L, respectively. The receptor binding experimental results exposed that FDTP demonstrated nanomolar
Ki value for binding to the D
4 receptor with several hundredfold selectivities towards dopamine D
2 and D
3 receptors. The lipophilicity of it is determined to be 0.85. In conclusion,
18F-FDTP is radiochemically synthesized and its preliminary
in vitrostudies indicate that
18F-FDTP shows promise as a potential imaging agent for dopamine D
4 receptor and further studies, such as
in vivodistribution and PET imaging studies, are needed to evaluate the new tracer.