Solid phase-supported reaction of N.C.A. H11CN with arabinose: a simplified automated synthesis of D-[1-11C]glucose

Abstract

A simplified, automated synthesis for D‐[1‐11C]glucose is described by the solid phase‐supported reaction of NH411CN with D‐arabinose on an Alumina N Sep‐Pak™. 11C‐cyanide reacted instantaneously to produce [1‐11C]aldonitriles. Reduction with Raney nickel in formic acid and semipreparative HPLC afforded D‐[1‐11C]glucose with radiochemical purity >95%. Compared with previously reported procedures a pH adjustment and rotary evaporation step is avoided resulting in a shortening of the synthesis time from 55 to 38 min. The radiochemical yield was 5–15% (2.5–8.5% non‐corrected) based on NH411CN. For a typical production starting with 20 GBq of NH411CN up to 500 MBq D[1‐11C]glucose was obtained at end of synthesis as a sterile, formulated solution. © 1998 John Wiley & Sons, Ltd.

[11C]HCN Radiochemistry: Recent Progress and Future Perspectives

“…In addition, the practice of umpolung tactics with cyano moiety has also made the electrophilic 11 C-cyanation occurred by using [ 11 C]cyanogen bromide ([ 11 C]CNBr) as the [ 11 C]cyanide source. [9] Many 11 C-labeled bioactive molecules have been synthesized using [ 11 C]cyanide as radiosynthon and have been successfully implemented in medical imaging research and even for disease diagnosis (Figure 4), such as [ 11 C] amino acids, [12][13][14]27] [ 11 C]deoxyglucose [28] and [ 11 C]glucose [29] for cancerous or normal tissue metabolism study, [ 11 C] spiroperidol [30] for dopamine system imaging by in vivo binding neuroleptic receptors, [ 11 C]octylamine [31] for MAO influenced aliphatic amine, [ 11 C]putrescine [32] for understanding the biochemistry of putrescine in tumor and surrounding tissues, [ 11 C] letrozole [33] for breast cancer therapy, [ 11 C]levetiracetam for SV2 A imaging that could be related to the neurologic disease, [34] and isotopologues of some drug substances such as [ 11 C]isoniazid, [35] [ 11 C]pyrazinamide [35] and [ 11 C]PT119 [36] for tuberculosis diagnostic imaging, disease staging, and therapeutic improvement. Lately, PET technology has been actively applied in green energy research, therefore plant hormones [37] and fatty acids [38] were developed for studying the plant development and disease defense mechanism.…”

“…[39] Due to the rates of transport and phosphorylation of [ 18 F]FDG in vivo is not the same as those of glucose, D-[1-11 C]glucose was developed to determine the real 'Lumped Constant' (LC) value of glucose [40] in normal and abnormal physical states in vivo and carry out the comparison with the [ 18 F]FDG results for glucose transport and phosphorylation. [29] Such a topic has been continually studied until now. [41] Previously, 11 C-labeled glucose radiosynthesis, on either position 1, [11,42] or position 6, [43] has been explored through either biosynthesis [42a-d] or specifically chemical labeling.…”

“…[11,42e-g] Bender and Gee adapted the classical Kiliani-Fisher method for mono-saccharides synthesis. [42g] The solid phase-supported radiosynthesis of D-[1-11 C]glucose was based upon a two-step synthetic method using [ 11 C]cyanide as radiosynthon, [29] CN trapped on the Sep-Pak) and high radiochemical purity (RCP, > 95 %). The entire synthesis took 38 min from EOB to end of synthesis (EOS) with a fully automated process.…”

“…The entire synthesis took 38 min from EOB to end of synthesis (EOS) with a fully automated process. [29] Ascorbic acid is an endogenous anti-oxidant. It plays an important role in maintaining redox balance in organisms.…”

“…The selection of 5-member ring sulfamidate derivative as 11 C-cyanation precursor raised the possibility of direct synthesis L-[4-11 C]asparagine. The adaption of an [ 11 C]HCN purification protocol, [29] removals of trace amount of H 2 O and excess NH 3 from [ 11 C]HCN/He stream, dramatically mitigated the racemization. Eventually, a facile two-step synthetic pathway using a 5-member ring sulfamidate precursor for the L-[4- 11 C]asparagine synthesis was developed, Figure 11C.…”