Radiolabeling of [11C]FPS-ZM1, a receptor for advanced glycation end products-targeting positron emission tomography radiotracer, using a [11C]CO2-to-[11C]CO chemical conversion

Aim: 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 A beta plaque formation. The development of a carbon-11 analog of FPS-ZM1 (N-benzyl-4-chloro-N-cyclohexylbenzamide, [C-11]FPS-ZM1), possessing nanomolar affinity for RAGE, may enable the imaging of RAGE for early AD detection. Methodology & results: Herein we report an optimized [C-11]CO2-to-[C-11]CO chemical conversion for the synthesis of [C-11]FPS-ZM1 and in vitro brain autoradiography. The [C-11]CO2-to-[C-11]CO conversion via C-11-silanecarboxylate derivatives was achieved with a 57% yield within 30 s from end of [C-11]CO2 delivery. [C-11]FPS-ZM1 was obtained with a decay-corrected isolated radiochemical yield of 9.5%. Conclusion: [C-11]FPS-ZM1 distribution in brain tissues of wild-type versus transgenic AD model mice showed no statistically significant difference and high nondisplaceable binding.