Strategy for improved [11 C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [11 C]DAA1106

Abstract Introduction The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [11 C]DAA1106 ([11 C] N -(2,5-dimethoxybenzyl)- N -(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. Methods A four-step synthetic route was devised to prepare DAA1123, the precursor for [11 C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [11 C]- O -methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [11 C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [11 C]CH3 I trapped. Evaluation of [11 C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. Results The standard solution method produced 2.6–5.2 GBq ( n =19) of [11 C]DAA1106, whilst the captive solvent method produced 1.6–6.3 GBq ( n =10) of [11 C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/μmol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [11 C]DAA1106. In vivo microPET [11 C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 μmol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. Conclusions A robust, high yielding captive solvent method of [11 C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model.