Radiolabeling of 11C-carbonyl groups of carbamates, oxazolidinones, ureas, and carboxylic acids can now be accomplished using [11C]CO2 (carbon-11, t1/2 = 20.4 min) generated directly from the cyclotron. These methods are complementary to the most common radiolabeling strategy using carbon-11, which is methylation using [11C]CH3I. This technology can be used to prepare libraries of labeled compounds that can be concurrently utilized to identify and carry out in vivo evaluation of potential 18F-labeled compounds.As an example of a new 11C-carboxylic acid that has been prepared, a metal-catalyzed [11C]CO2-fixation reaction was applied to label bexarotene, an anti-cancer drug that has shown potential for the treatment of Alzheimer's disease in preclinical models. The radiolabeling was carried out in a single step using an aryl boronic ester precursor mixed with CuI, TMEDA, and a fluoride-releasing additive, TBAT, with [11C]CO2. [11C]Bexarotene was produced in 15% isolated radiochemical yield (non-decay-corrected) and 0.3 Ci/�mol specific activity. PET imaging in a nonhuman primate showed modest whole brain uptake (SUVmax= 0.8), and regional uptake consistent with retinoid X receptor distribution.By virtue of the operational simplicity and convergent radiolabeling approach, libraries of candidate 11C-radiotracers for the enzyme fatty acid amide hydrolase (FAAH) have been prepared and assayed in vivo. In these reactions, [11C]CO2 is trapped in a solution of a fixation base with precursor amine, and dehydrated by POCl3 to generate 11C-isocyanates, key intermediates for radiosynthesis of complex molecules. Nucleophiles such as phenols and aliphatic or aromatic amines rapidly add to 11C-isocyanates to generate 11C-carbamates and -ureas, respectively. Using [11C]CO2-fixation as a discovery platform, a fluorine-18 (t1/2 = 109.7 min) labeled FAAH radiotracer, [18F]DOPP, has been identified and imaged in nonhuman primate. [18F]DOPP shows rapid high brain uptake (SUVmax > 2.0), binding consistent with known FAAH distribution, and dose-dependent blocking with a known FAAH inhibitor, URB597.

<sup>11</sup>CO<sub>2</sub>-fixation for discovery and development of novel carbon-11 and fluorine-18 labeled radiotracers

248th National Meeting (2014)

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11CO2-fixation for discovery and development of novel carbon-11 and fluorine-18 labeled radiotracers

¹¹CO₂-fixation for discovery and development of novel carbon-11 and fluorine-18 labeled radiotracers