Radiolabeling of [C]FPS-ZM1, a receptor for advanced glycation end products-targeting positron emission tomography radiotracer, using a [C]CO-to-[C]CO chemical conversion.

The receptor for advanced glycation end products (RAGE) is a viable target for early Alzheimer's disease (AD) diagnosis using positron emission tomography (PET) as RAGE overexpression precedes Aβ plaque formation. The development of a carbon-11 analog of FPS-ZM1 (N-benzyl-4-chloro-N-cyclohexylbenzamide, [C]FPS-ZM1), possessing nanomolar affinity for RAGE, may enable the imaging of RAGE for early AD detection. Herein we report an optimized [C]CO-to-[C]CO chemical conversion for the synthesis of [C]FPS-ZM1 and brain autoradiography. The [C]CO-to-[C]CO conversion via C-silanecarboxylate derivatives was achieved with a 57% yield within 30 s from end of [C]CO delivery. [C]FPS-ZM1 was obtained with a decay-corrected isolated radiochemical yield of 9.5%. [C]FPS-ZM1 distribution in brain tissues of wild-type versus transgenic AD model mice showed no statistically significant difference and high nondisplaceable binding.