Investigation of SN2 [11C]cyanation for base-sensitive substrates: an improved radiosynthesis of l-[5-11C]-glutamine

• Published in: Amino acids 2015-03, Vol.47 (3), p.525-533
• Main Authors: Gleede, Tassilo, Riehl, Barbara, Shea, Colleen, Kersting, Lena, Cankaya, Aylin Sibel, Alexoff, David, Schueller, Michael, Fowler, Joanna S., Qu, Wenchao
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Carbon Isotopes - chemistry; Glutamine - chemical synthesis; Glutamine - chemistry; Humans; Isotope Labeling - methods; Life Sciences; Neurobiology; Original Article; Proteomics; Radiochemistry - methods
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-014-1883-z

Carbon-11 (β + emitter, t 1/2  = 20.4 min) radiolabeled l -glutamine is a potentially useful molecular imaging agent that can be utilized with positron emission tomography for both human oncological diagnosis and plant imaging research. Based upon a previously reported [ 11 C]cyanide end-capping labeling method, a systematic investigation of nucleophilic cyanation reactions and acidic hydrolysis reaction parameters, including base, metal ion source, phase transfer catalyst, solvent, reaction temperature and reaction time, was conducted. The result was a milder, more reliable, two-step method which provides l -[5- 11 C]-glutamine with a radiochemical yield of 63.8 ± 8.7 % (range from 51 to 74 %, n  = 10) with >90 % radiochemical purity and >90 % enantiomeric purity. The total synthesis time was 40–50 min from the end of bombardment. In addition, an Fmoc derivatization method was developed to measure the specific activity of this radiotracer.