Synthesis of 18F-Labeled FC-119S and Its Tosyl Precursor

Abstract

Animal models of Alzheimer's disease (AD) are essential for developing therapeutics and evaluating the efficacy of new drug candidates. Positron emission tomography (PET) is a useful method to monitor a major hallmark of the onset of AD, namely, the deposition of amyloid β peptide (Aβ) in the brain. [¹⁸F]FC-119S (1), a 2-pyridylbenzothiazole analog, has been applied as a radiotracer for PET visualization of Aβ plaques in an AD model, the 5xFAD mouse. Here, we present an alternative method for the automated synthesis of ¹⁸F-labeled 1 as a radiotracer for our animal PET studies. The first attempt at synthesizing ¹⁸F-labeled 1 using a mesyl precursor afforded desired product 1, although a nonfluorinated mesyl byproduct was eluted prior to 1 during purification by semipreparative high-performance liquid chromatography. An alternative synthesis using a tosyl precursor was applied to delay the elution of a nonfluorinated byproduct during chromatographic purification. As a result, ¹⁸F-labeled 1 was eluted without proximate byproducts during chromatographic purification, and routine production of ¹⁸F-labeled 1 was achieved for our AD studies using animal models.