Abstract
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Objectives [18F]T807 has been proved to be a promising PHF-tau tracer for studying AD in humans [1, 2]. However, the reported methods for [18F]T807 production were somewhat complicated [2,3] . In order to use this tracer for human studies, we have improved its synthesis and studied its whole-body biodistribution in mice and monkeys before human studies are undertaken.
Methods The [18F]T807 was synthesized in a FXFN module as reported previously with some modifications [3]. Briefly, fluorination of N-t-Boc protected precursor (1) with K[18F]/K2.2.2 in DMSO at 130 0C for 10-20 min gave the intermediate (2). A solution of 1N HCl(aq) was added to (2) and the mixture was heated at 90 0C for 5-10 min . Following neutralizion with 2N NaOAc and buffer, the crude product was purified with a semi-preparative HPLC to give [18F]T807 (Scheme 1). For animal study, fasten male ICR mice (n=4) and male Formosa rock monkeys (n=2) were injected with a bolus of about 200 μCi and 2.6 mCi of [18F]T807, respectively. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using the OLINDA/EXM software.
Results The radiochemical yield of [18F]T807 synthesized by this method was 13±4 % (EOS, n>3) in a synthesis time of ~70 min from EOB. Both the chemical and radiochemical purity were >95 % with a specific activity of 4.1±1.4 Ci/μmol. Whole-body biodistribution in mice showed that the radioactivity in the gallbladder and lower large intestine increased with time. In contrast, there was no significant [18F]T807 uptake in the large intestine of monkeys. The effective dose of [18F]T807 in mice and monkey were 94±19 and 20±0 μSv/MBq, respectively.
Conclusions With the improved radiosynthesis method, [18F]T807 could be reliably produced for preclinical and clinical studies. Additionally, whole-body biodistribution in mice and monkeys showed that [18F]T807 is safe for human studies.