Open AccessSynthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2
Author(s) -
Andrew V. Mossine,
Allen F. Brooks,
Isaac M. Jackson,
Carole Quesada,
Phillip Sherman,
Erin L. Cole,
David J. Donnelly,
Peter J. H. Scott,
Xia Shao
Publication year - 2016
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.6b00163
Subject(s) - chemistry , radiosynthesis , radiochemistry , isotopic labeling , cycloaddition , positron emission tomography , bromide , yield (engineering) , combinatorial chemistry , organic chemistry , nuclear medicine , catalysis , medicine , materials science , metallurgy
Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.