Direct one-step labeling of cysteine residues on peptides with [(11)C]methyl triflate for the synthesis of PET radiopharmaceuticals.
Radiolabeled peptides have emerged as an attractive platform for the diagnostic and therapeutic oncology. However, the (11)C-radiolabeling of peptides for positron emission tomography (PET) has been poorly explored, owing to the relatively short half-life of carbon-11 (t 1/2 = 20.3 min) and time-consuming multi-step radiochemical reactions. Existing methods have found limited use and are not routinely encountered in the production of radiotracers. Herein, we propose a facile one-step direct (11)C-methylation of cysteine residues in peptides using [(11)C]methyl triflate under ambient temperatures (20 °C) and short reaction times, on the order of seconds. Good regioselectivity of this method was demonstrated by HPLC in a simple peptide (glutathione, GSH) and a more complex test decapeptide (Trp-Tyr-Trp-Ser-Arg-Cys-Lys-Trp-Thr-Gly) bearing multiple nucleophilic sites. In addition, we extend this method towards the synthesis of [(11)C]Cys(Me)-[Tyr(3)-octreotate] as a demonstration of applicability for peptides of biological interest. This octreotate derivative was obtained in non-decay-corrected radiochemical yields of 11 ± 2 % (n = 3) with a synthesis time of approx. 30 min.
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
Joshua
J
Chin
Matthew
M
Vesnaver
Vadim
V
Bernard-Gauthier
Erin
E
Saucke-Lacelle
Björn
B
Wängler
Carmen
C
Wängler
Ralf
R
Schirrmacher
D002250:Carbon Radioisotopes / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D007553:Isotope Labeling; D008698:Mesylates / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
D002250:Carbon Radioisotopes; D008698:Mesylates; D010455:Peptides; D019275:Radiopharmaceuticals; C078465:methyl triflate; D003545:Cysteine