Development of Selective Carbon-11 Radioligands for Target-Based PET Molecular Imaging in Oncology, Cardiology and Neurology

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Background

The positron emission tomography (PET) molecular imaging technique is a remarkable tool in medical diagnosis, biomedical research, and clinical applications. PET is mainly used to study therapeutic drug development, doses regimen, metabolism, distribution, and drug plasma concentrations of new drug candidates in clinical investigations. The raise of PET molecular imaging with selective radioligands have been exponentially increasing due to many advances in biomedical, and clinical research. MEDrays Intell nuclear medicine world market report 2019 estimated the usage of radiopharmaceuticals with 39.1 % and radiodiagnostics with 7.0% within a span of five years from 2020-2025. The selective radioligands provide target-specific information in various disease conditions like oncology, cardiology, and neurology by measuring rates of biological processes with PET relate to its physiological changes in the living subjects, thus it reveals the disease progression as well as speed up the clinical trials. Carbon-11 is considered a promising radiotracer that can provide target-related information to understand its pharmacology, and physiology of the disease status. Several methodologies were developed to synthesize various selective carbon-11 (t1/2 = 20.4 min) radioligands, and the majority of them are heterocyclic derivatives where the carbon-11 radionuclide is inserted at different positions using the primary or secondary carbon-11 precursors. The [11C]CO2 and [11C]CH4 are considered as primary carbon-11 precursors, whereas as [11C]CO, [11C]CHO, [11C]COCl, [11C]CH3I, [11C]CCl4, [11C]HCN, and [11C]CH3OTf etc. are considered as secondary precursors. These primary and secondary carbon-11 precursors are being used to generate carbon-11 radiotracers. Several carbon-11 radiotracers are being used currently in various biomedical research programs (preclinical studies) as well as in clinical PET centers (clinical studies), a few examples include [11C]methionine for amino acid transport and protein synthesis, 2-[11C]thymidine for tumor cell proliferation, [11C]acetate for the tricarboxylic acid cycle, [11C]meta-hydroxyephedrine for presynaptic catecholamine reuptake, [11C]raclopride for dopamine receptor densities, [11C]methylspiperone for 5-HT2 receptor density, and [11C]PK11195 for neuronal microglial activation.

Considering the importance of the PET molecular imaging with selective radioligands in various disease conditions, we dedicate this Research Topic in Frontiers in Medicine to summarize the development of selective carbon-11 radioligands for target-based PET molecular imaging in oncology, cardiology & neurology.

The themes to be covered in this Research Topic are, but not limited to, the following:
• The radiosynthesis and methodologies of carbon-11 radioligands.
• PET molecular imaging applications in oncology, cardiology and neurology.
• Development of protocols and automated synthesis of carbon-11 radioligands.
• In vitro radioligand assays, autoradiography studies, Immunohistochemistry, preclinical and clinical PET imaging studies.

Keywords: carbon-11, radioligands, positron emission tomography, molecular imaging techniques, oncology, cardiology, neurology.

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