Abstract
1096
Introduction: The development of innovative radiolabeling strategies with carbon-11 is important for future PET tracer development. 11C-methylation with [11C]CH3I/[11C]CH3OTf is the most popular method currently used for 11C-labeling of various organic molecules via nucleophilic C-, N-, O-, S-alkylation reactions, as well as precious metal catalyzed aryl-methylation reaction, etc. Relying upon our recently developed fluoride-desilylation mediated (FDSM) 11C-carboxylation approach, we further investigated [11C]CH3I/[11C]CH3OTf as radiolabeling synthons to broaden its application scope.
Methods: The experimental conditions for 11C-methylation using the FDSM approach were optimized including the fluoride source, solvent, reaction temperature, etc. Next, twenty organosilane reagents were tested to illustrate the amenability of FDSM 11C-methylation approach. The syntheses of three 11C-labeled bioactive molecules were explored to further demonstrate the practical applicability of FDSM 11C-methylation method.
Results: Fifteen 11C-labeled molecules (with [11C]CH3- group attached to oxygen, sulfur, nitrogen and carbon atoms) were synthesized under mild reaction conditions (DMF, r.t. to 100 oC, 2 - 5 min) in acceptable to excellent radiochemical conversion yields (RCC, from 33% to 93%). In addition, three biologically and clinically interesting molecules, [3-11C]propiophenone, [3-11C]ibuprofen and [11C]raclopride, were successfully synthesized using the FDSM 11C-methylation method with radiochemical yield (RCY, n = 3) at 68.2 ± 8.9%, 26.6 ± 0.6% & 27.8 ± 2.2%, respectively.
Conclusions: A robust and novel FDSM 11C-methylation method was developed. A variety of 11C-labeled organic molecules have been synthesized by this simplified, highly reproducible approach, which offered an alternative solution for [11C]CH3I/[11C]CH3OTf based radiochemistry. Acknowledgements: This work was supported by the Radiology Department, Weill Cornell Medicine (WCM) (Internal research fund for W.Q. and B.H.). Both Howard Sheh and Calvin Lom are acknowledged for cyclotron operation to supply [11C]CO2 radioactivity. Supplemental Material