New methodologies for the preparation of carbon-11 labeled radiopharmaceuticals

Abstract

PurposeThis short review aims to cover the more recent and promising developments of carbon-11 (11C) labeling radiochemistry and its utility in the production of novel radiopharmaceuticals, with special emphasis on methods that have the greatest potential to be translated for clinical positron emission tomography (PET) imaging.MethodsA survey of the literature was undertaken to identify articles focusing on methodological development in 11C chemistry and their use within novel radiopharmaceutical preparation. However, since 11C-labeling chemistry is such a narrow field of research, no systematic literature search was therefore feasible. The survey was further restricted to a specific timeframe (2000–2016) and articles in English.ResultsFrom the literature, it is clear that the majority of 11C-labeled radiopharmaceuticals prepared for clinical PET studies have been radiolabeled using the standard heteroatom methylation reaction. However, a number of methodologies have been developed in recent years, both from a technical and chemical point of view. Amongst these, two protocols may have the greatest potential to be widely adapted for the preparation of 11C-radiopharmaceuticals in a clinical setting. First, a novel method for the direct formation of 11C-labeled carbonyl groups, where organic bases are utilized as [11C]carbon dioxide-fixation agents. The second method of clinical importance is a low-pressure 11C-carbonylation technique that utilizes solvable xenon gas to effectively transfer and react [11C]carbon monoxide in a sealed reaction vessel. Both methods appear to be general and provide simple paths to 11C-labeled products.ConclusionRadiochemistry is the foundation of PET imaging which relies on the administration of a radiopharmaceutical. The demand for new radiopharmaceuticals for clinical PET imaging is increasing, and 11C-radiopharmaceuticals are especially important within clinical research and drug development. This review gives a comprehensive overview of the most noteworthy 11C-labeling methods with clinical relevance to the field of PET radiochemistry.

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…Thes hort half-life of 11 Cr equires ah ighly efficient transformation, which usually occurs on the ultimate or penultimate step to maximize the use of rapidly decaying radioactivity.C omplementary to previous reviews on 11 C, [5,[9][10][11][12][13][14] we highlight some recent developments and breakthroughs in 11 Cc hemistry,w ith an emphasis on commonly used synthons and novel building blocks (Scheme 1). Thes hort half-life of 11 Cr equires ah ighly efficient transformation, which usually occurs on the ultimate or penultimate step to maximize the use of rapidly decaying radioactivity.C omplementary to previous reviews on 11 C, [5,[9][10][11][12][13][14] we highlight some recent developments and breakthroughs in 11 Cc hemistry,w ith an emphasis on commonly used synthons and novel building blocks (Scheme 1).…”

“…Thes hort half-life of 11 Cr equires ah ighly efficient transformation, which usually occurs on the ultimate or penultimate step to maximize the use of rapidly decaying radioactivity.C omplementary to previous reviews on 11 C, [5,[9][10][11][12][13][14] we highlight some recent developments and breakthroughs in 11 Cc hemistry,w ith an emphasis on commonly used synthons and novel building blocks (Scheme 1). The broad application and rapid advances of PET has led to an increased demand for new radiochemical methods to synthesize highly specific molecules bearing positron-emitting radionuclides.T his Review provides an overview of commonly used labeling reactions through examples of clinically relevant PET tracers and highlights the most recent developments and breakthroughs over the past decade,w ith afocus on 11 C, 18 F, 13 3 Ii sb yf ar the most frequently used 11 C-labeling agent. [5,12] Positron emission tomography (PET) is amolecular imaging technology that provides quantitative information about function and metabolism in biological processes in vivo for disease diagnosis and therapyassessment.…”

“…Most noteworthy is that these [ 11 C]CO 2 fixation reactions are simple,carried out in one pot, generally require no heating or cooling,a nd are easily automated. [10][11][12][13][14] Pd-mediated cross-coupling reactions between aryl/benzylic/methyl halides and [ 11 C]CO can provide 11 C-labeled carboxylic acids or esters in the presence of hydroxides or alcohols,r espectively (Scheme 5A1). [9,12] Rather than 11 C-carbonylation, Billard and co-workers developed as imple method to achieve 11 C-methylation of amines with [ 11 C]CO 2 under reducing conditions.…”

The Emergence of Carbon Isotope Exchange

“…Further utility for carbon-11 labelling of in vivo imaging radiotracers [10] could be foreseen because of the late-stage and high isotopic enrichment assets of this promising CIE approach. Further utility for carbon-11 labelling of in vivo imaging radiotracers [10] could be foreseen because of the late-stage and high isotopic enrichment assets of this promising CIE approach.…”

Das aufkommende Konzept des Kohlenstoffisotopenaustauschs

“…Ein weiterer vorhersehbarer Nutzen ist fürd ie 11 C-Markierung von Radiotracern fürdie In-vivo-Bildgebung, [10] aufgrund der Eignung dieses CIE-Ansatzes fürs p äte Synthesestufen und hohe Isotopenanreicherungen. Es besteht kein Zweifel daran, dass sich zahlreiche Forschungsarbeiten künftig der Entdeckung neuer CIE-Reaktionen widmen werden, um den Anwendungsbereich zu erweitern und multiplen Isotopeneinbau zu ermçglichen.…”