Radiolabeling of [ ¹¹ C]FPS-ZM1, a Receptor for Advanced Glycation End products-targeting Positron Emission Tomography radiotracer, Using a [ ¹¹ C]CO ₂ -to-[ ¹¹ C]CO Chemical Conversion

Abstract

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