State of Art in 11C Labelled Radiotracers Synthesis

Abstract

Positron Emission Tomography has become a powerful scientific and clinical tool probing biochemical processes in the human body. Their clinical applications have proven to be vital in the evaluation and diagnosis of diseases. This is due, in large part, to advances in instrumentation and synthetic chemistry. Carbon-11 is a valuable radionuclide in PET as it virtually permits the synthesis of radiolabelled versions of any compound of interest. The syntheses with carbon-11 present several features: limited number of labelled precursors, sub-micromolar amounts of the starting materials, and a need for the introduction of the radioisotope as late as possible in the synthesis. All of these reasons have restricted complex radiosyntheses. The short half-life of carbon-11 (20.4 min) requires the rapid preparation and purification of carbon-11 labelled molecules. Those have to be carried out immediately before use from cyclotron produced precursors ([11C]CO2, [11C]CO, [11C]CH4) or reagents rapidly prepared from them ([11C]CH3I, [11C]COCl2, [11C]HCN). As a consequence carbon-11 has been underused compared to fluorine-18. However, because of the increasing molecular complexity and diversity of biologically active compounds, there is a need for new methodologies giving access in short time and high yield to radioactive (11)C-probes. The aim of this review is to emphasize the methodologies used in this field and to give a comprehensive overview of the numerous advances, which occurred over the past decade. In addition, for each labelling technique or reaction reported, a special attention has been brought to classify the applications in function of the targeted medical domain.

Recent Advances in Carbon Dioxide Capture, Fixation, and Activation by using N‐Heterocyclic Carbenes

“…[143] Taking the carboxylation of aryl-and alkenyl-Scheme 10. [144][145][146] Equation (17) shows the model carboxylation reaction to produce [ 11 C]carboxylates. In addition, Riss et al [143] found an efficient method to produce [ 11 C]carboxylates that might display high functionalgroup tolerance; 11 C has important applications in medicine.…”

“…It is a valuable radiolabel for noninvasive imaging with positron emission tomography (PET) radiotracers, because carbon is present in nearly all biochemicals and drug candidates, despite its short half-life. [144][145][146] Equation (17) shows the model carboxylation reaction to produce [ 11 C]carboxylates. The Cu-NHC mixture was also able to trap 11 CO 2 exceedingly well.…”

4-[18F]Fluorophenylpiperazines by Improved Hartwig-Buchwald N-Arylation of 4-[18F]fluoroiodobenzene, Formed via Hypervalent λ3-Iodane Precursors: Application to Build-Up of the Dopamine D4 Ligand [18F]FAUC 316

“…This was recently also recognized by awarding the Nobel Prize to Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki in 2010 [2]. Therefore, it is remarkable that application of this method in radiosyntheses using short-lived radionuclides like 11 C (t 1/2 = 20.4 min) or 18 F (t 1/2 = 109.7 min) is still an exception and only a few examples of its use are described [3,4,5]. Cross-coupling reactions allow for a quick synthesis of many structure motives of biomolecules relevant for non-invasive diagnostic imaging techniques such as positron emission tomography (PET).…”

11CO2 fixation: a renaissance in PET radiochemistry

“…2 Still, the most common strategy used is methylation using [ 11 C]methyl iodide or [ 11 C]methyl triflate. 3,4 Carbon-11 labelled carbon dioxide is the product of proton bombardment of nitrogen-14 in the presence of small amounts of oxygen by the 14 N(p,α) 11 C nuclear reaction. Most often, [ 11 C]CO 2 is transformed to more reactive species, such as the aforementioned methylating reagents, to facilitate radiolabelling.…”