Neprilysin, also known as neutral endopeptidase, is a cell surface membrane metalo-endopeptidase that cleaves various peptides. Altered neprilysin expression has been correlated with various cancers and cardiovascular diseases. In this work, we present the radiosynthesis of the novel O-11 C-methylated deriva-is an analog of sacubitril where the alkyl ester is a 11 C-methyl instead of an ethyl. [ 11 C]MeOLBQ was produced in a one-pot two-step synthesis. The O-11 C-methylation of the pentanoic acid part was done with [ 11 C] methyl triflate followed by the deprotection of the tert-butyl ester precursor in acidic conditions. [ 11 C]MeOLBQ ([ 11 C]7) was produced in 9.5 ± 2.5% RCY (25 ± 6% decay-corrected from [ 11 C]CO 2 , n = 3) high molar activity 348 ± 100 GBq/μmol (9425 ± 2720 mCi/μmol) at EOS, in high chemical (>95%) and radiochemical (>99%) purities. The total synthesis time including HPLC purification and reformulation was 29 minutes. To our knowledge, this is the first PET-labeled analog of the clinically used NEP inhibitor sacubitril.
K E Y W O R D Scarbon-11, 11 C-esterification, heart failure, natriuretic peptides, radiosynthesis, sacubitril
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