Development of 2-Deoxy-2-[F-18]fluororibose for Positron Emission Tomography Imaging Liver Function in Vivo

作者：Evdokimov Nikolai M^*; Clark Peter M; Flores Graciela; Chai Timothy; Faull Kym F; Phelps Michael E; Witte Owen N; Jung Michael E

来源：Journal of Medicinal Chemistry, 2015, 58(14): 5538-5547.

DOI：10.1021/acs.jmedchem.5b00569

Life-threatening: acute liver failure can be triggered, by a variety of factors,, including common drugs such as acetaminophen,. Positron emission tomography (BET) is rarely used to monitor liver function, In part because of a lack of specific imaging agents for liver function.. Here we report a new PET probe, 2-deoxy-2[F-18]fluororibose ([F-18]-2-DFR), for use in imaging liver function. [F-18]-2-DFR was synthesized and validated as a competitive substrate for the ribose salvage pathway. [F-18]-2-DFR was prepared through an efficient late Stage radiofluorination. The desired selectivity of fluorination was achieved using an unorthodox protecting group on the precursor, which could withstand harsh S(N)2 reaction conditions with no side reactions.[F-18,]-2-DFR accumulated preferentially in the liver and was metabolized by the same enzymes, as ribose. [F-18]-2-DFR could distinguish between healthy liver and, liver damaged by acetaminophen. [(18)]-2-DFR is expected to-be a useful PET probe for imaging and quantifying liver functions in vivo, with likely significant clinical utility.

• 出版日期2015-7-23