Single-Step High-Yield Radiosynthesis and Evaluation of a Sensitive, 18F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET

Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared, and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new F-18-labeled PBR radioligand, namely [F-18]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([F-18]9). [F-18]9 was produced easily through a single and highly efficient step, the reaction of [F-18]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [F-18]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [F-18]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [F-18]2-fluoro-N-(2-phenoxyphenyl)acetamide ([F-18]11). [F-18]9 is a promising radioligand for future imaging of PBR in living human brain.