The chemistry of labeling heterocycles with carbon-11 or fluorine-18 for biomedical imaging

Abstract Over the last half-century, the molecular imaging technique of positron emission tomography (PET) has emerged as an important tool for biomedical research, drug development and medical diagnosis. The power of PET derives from its utilization of radiotracers that can report specific information on pharmacology, biochemistry, and physiology. Many of these radiotracers are heterocycles that have been labeled with a short-lived cyclotron-produced radioisotope, either carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 109.8 min). This review addresses the chemical challenges to be met in producing PET radiotracers with these radioisotope labels at heterocyclic moieties and the methods now available for doing so.

• Publication year

  2020

• Venue

  Unknown venue

• Publication date

  Unknown publication date

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/bs.aihch.2019.11.005
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Positron-emitting radionuclides for applications, with special emphasis on their production methodologies for medical use

  2019cited by this paper
• First Human Imaging Studies with the EXPLORER Total-Body PET Scanner*

  2019cited by this paper
• [18 F]Ethenesulfonyl Fluoride as a Practical Radiofluoride Relay Reagent.

  2019cited by this paper
• Carbon monoxide : advances in production and application to PET radiotracer development over the past 15 years

  2019cited by this paper
• Development, Optimization, and Scope of the Radiosynthesis of 3/5-[18F]Fluoropyridines from Readily Prepared Aryl(pyridinyl) Iodonium Salts: The Importance of TEMPO and K2CO3

  2019cited by this paper
• Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation.

  2019cited by this paper
• Minimalist approach meets green chemistry: Synthesis of 18 F- labeled (hetero)aromatics in pure ethanol.

  2019cited by this paper
• Copper-Mediated Aminoquinoline-Directed Radiofluorination of Aromatic C-H Bonds with K18 F.

  2019cited by this paper
• Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18.

  2019cited by this paper
• Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a "Tail Switching" Strategy on a Piperazinyl Azetidine Skeleton.

  2019cited by this paper
• Bioconjugated arylpalladium complexes on solid supports for a convenient last-step synthesis of 11C-labelled tracers for positron emission tomography.

  2019cited by this paper
• Nucleophilic 18F-Fluorination of Anilines via N-Arylsydnone Intermediates

  2018cited by this paper
• Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic 18F-Fluorination

  2018cited by this paper
• Copper(II)-Mediated [11C]Cyanation of Arylboronic Acids and Arylstannanes.

  2018cited by this paper
• Development and optimization of a novel automated loop method for production of [11C]nicotine.

  2018cited by this paper
• An efficient new method for the synthesis of 3-[18 F]fluoro-4-aminopyridine via Yamada-Curtius rearrangement.

  2018cited by this paper
• Palladium(ii)-mediated rapid 11C-cyanation of (hetero)arylborons.

  2018cited by this paper
• "In-loop" [11 C]CO2 fixation: Prototype and proof of concept.

  2018cited by this paper
• Automated Synthesis of (rac)‐, (R)‐, and (S)‐[18F]Epifluorohydrin and Their Application for Developing PET Radiotracers Containing a 3‐[18F]Fluoro‐2‐hydroxypropyl Moiety

  2018cited by this paper
• Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure

  2018cited by this paper
• Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state

  2018cited by this paper
• Rapid synthesis of maleimide functionalized fluorine-18 labeled prosthetic group using "radio-fluorination on the Sep-Pak" method.

  2018cited by this paper
• Hypervalent Iodine Compounds as Precursors for Biomedical Radiotracers

  2018cited by this paper
• Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways

  2018cited by this paper
• Radiosynthesis and in vivo evaluation of a fluorine-18 labeled pyrazine based radioligand for PET imaging of the adenosine A2B receptor.

  2018cited by this paper
• Investigation of an 18F-labelled Imidazopyridotriazine for Molecular Imaging of Cyclic Nucleotide Phosphodiesterase 2A

  2018cited by this paper
• Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation.

  2018cited by this paper
• In Vitro and in Vivo Evaluation of 11C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies.

  2018cited by this paper
• 18F-Trifluoromethylation of Unmodified Peptides with 5-18F-(Trifluoromethyl)dibenzothiophenium Trifluoromethanesulfonate.

  2018cited by this paper
• Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry

  2018cited by this paper
• Hypervalent aryliodine compounds as precursors for radiofluorination.

  2018cited by this paper
• Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

  2018cited by this paper
• [18F]fluoro-benziodoxole: a no-carrier-added electrophilic fluorinating reagent. Rapid, simple radiosynthesis, purification and application for fluorine-18 labelling.

  2018cited by this paper
• Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation

  2017cited by this paper
• Radiosynthesis and biological evaluation of the new PDE10A radioligand [18 F]AQ28A.

  2017cited by this paper
• Synthesis of [18 F]Fluoroarenes by Nucleophilic Radiofluorination of N-Arylsydnones.

  2017cited by this paper
• Radiofluorination of a NHC-PF5 adduct: toward new probes for 18F PET imaging.

  2017cited by this paper
• Development of a 18F-Labeled Radiotracer with Improved Brain Kinetics for Positron Emission Tomography Imaging of Translocator Protein (18 kDa) in Ischemic Brain and Glioma.

  2017cited by this paper
• 18F-Deoxyfluorination of Phenols via Ru π-Complexes

  2017cited by this paper
• Development of [11C]vemurafenib employing a carbon-11 carbonylative Stille coupling and preliminary evaluation in mice bearing melanoma tumor xenografts

  2017cited by this paper
• [11C]AZ10419096 - a full antagonist PET radioligand for imaging brain 5-HT1B receptors.

  2017cited by this paper
• Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands.

  2017cited by this paper
• [11 C]Fluoroform, a Breakthrough for Versatile Labeling of PET Radiotracer Trifluoromethyl Groups in High Molar Activity.

  2017cited by this paper
• A useful PET probe [11C]BU99008 with ultra-high specific radioactivity for small animal PET imaging of I2-imidazoline receptors in the hypothalamus.

  2017cited by this paper
• Preparation of [18F]-NHC-BF3 conjugates and their applications in PET imaging

  2017cited by this paper
• Microfluidic radiosynthesis of [18F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

  2017cited by this paper
• Use of carbon-11 labelled tool compounds in support of drug development.

  2017cited by this paper
• Consensus nomenclature rules for radiopharmaceutical chemistry - Setting the record straight.

  2017cited by this paper
• Cu-Mediated C–H 18F-Fluorination of Electron-Rich (Hetero)arenes

  2017cited by this paper
• Nucleophilic 18F‐Labeling of Spirocyclic Iodonium Ylide or Boronic Pinacol Ester Precursors: Advantages and Disadvantages

  2017cited by this paper
• Instantaneous Conversion of [11C]CO2 to [11C]CO via Fluoride‐Activated Disilane Species

  2017cited by this paper
• Last-Step Pd-Mediated [11C]CO Labeling of a Moxestrol-Conjugated o-Iodobenzyl Alcohol: From Model Experiments to in Vivo Positron Emission Tomography Studies.

  2017cited by this paper
• [11C]Cyanation of arylboronic acids in aqueous solutions.

  2017cited by this paper
• Quinuclidine and DABCO Enhance the Radiofluorinations of 5-Substituted 2-Halopyridines.

  2017cited by this paper
• Radiosynthesis and in Vivo Evaluation of Neuropeptide Y5 Receptor (NPY5R) PET Tracers.

  2016cited by this paper
• A mild, rapid synthesis of freebase [11C]nicotine from [11C]methyl triflate.

  2016cited by this paper
• (18)F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography.

  2016cited by this paper
• Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain

  2016cited by this paper
• Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase

  2016cited by this paper
• Synthesis of meta-substituted [(18)F]3-fluoro-4-aminopyridine via direct radiofluorination of pyridine N-oxides.

  2016cited by this paper
• A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging

  2016cited by this paper
• Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines.

  2016cited by this paper
• Synthesis and pre-clinical evaluation of a [18F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression

  2016cited by this paper
• Low‐Pressure Radical 11C‐Aminocarbonylation of Alkyl Iodides through Thermal Initiation

  2016cited by this paper
• Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging.

  2016cited by this paper
• Alkyl Iodides and [11C]CO in Nickel‐Mediated Cross‐Coupling Reactions: Successful Use of Alkyl Electrophiles containing a β Hydrogen Atom in Metal‐Mediated [11C]Carbonylation

  2016cited by this paper
• Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent 18F-Labeled Ligand ([18F]UCB-H).

  2016cited by this paper
• Automated and efficient radiosynthesis of [(18)F]FLT using a low amount of precursor.

  2016cited by this paper
• Concerted nucleophilic aromatic substitution with 19F− and 18F−

  2016cited by this paper
• Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging.

  2016cited by this paper
• High-yielding, automated production of 3'-deoxy-3'-[(18)F]fluorothymidine using a modified Bioscan Coincidence FDG reaction module.

  2015cited by this paper
• Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous medium.

  2015cited by this paper
• Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.

  2015cited by this paper
• Radiosynthesis and evaluation of N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(4-fluorophenyl)thiazol-2-yl]-1-[11C]carboxamide for in vivo positron emission tomography imaging of fatty acid amide hydrolase in brain

  2015cited by this paper
• Development of indazolylpyrimidine derivatives as high-affine EphB4 receptor ligands and potential PET radiotracers.

  2015cited by this paper
• An efficient and practical synthesis of [2-(11)C]indole via superfast nucleophilic [(11)C]cyanation and RANEY® Nickel catalyzed reductive cyclization.

  2015cited by this paper
• Discovery of a high affinity and selective pyridine analog as a potential positron emission tomography imaging agent for cannabinoid type 2 receptor.

  2015cited by this paper
• General last-step labeling of biomolecule-based substrates by [12C], [13C], and [11C] carbon monoxide.

  2015cited by this paper
• Synthesis of a PET tau tracer [(11)C]PBB3 for imaging of Alzheimer's disease.

  2015cited by this paper
• Rapid and Efficient Conversion of (11) CO2 to (11) CO through Silacarboxylic Acids: Applications in Pd-Mediated Carbonylations.

  2015cited by this paper
• Carbon-11 radiolabelling of organosulfur compounds: (11) C synthesis of the progesterone receptor agonist tanaproget.

  2015cited by this paper
• Development of subnanomolar radiofluorinated (2-pyrrolidin-1-yl)imidazo[1,2-b]pyridazine pan-Trk inhibitors as candidate PET imaging probes

  2015cited by this paper
• 11C-carbonylation reactions using gas–liquid segmented microfluidics

  2015cited by this paper
• Pd(0)-mediated [11C]carbonylation of aryl and heteroaryl boronic acid pinacol esters with [11C]carbon monoxide under ambient conditions and a facile process for the conversion of [carbonyl-11C]esters to [carbonyl-11C]amides

  2015cited by this paper
• [(18)F]-NHC-BF3 adducts as water stable radio-prosthetic groups for PET imaging.

  2015cited by this paper
• Targeted fluorination with the fluoride ion by manganese-catalyzed decarboxylation.

  2015cited by this paper
• Dihydroquinoline Carbamate Derivatives as "Bio-oxidizable" Prodrugs for Brain Delivery of Acetylcholinesterase Inhibitors: [¹¹C] Radiosynthesis and Biological Evaluation.

  2015cited by this paper
• A novel 18F-labelled high affinity agent for PET imaging of the translocator protein

  2015cited by this paper
• One-Pot Two-Step Radiosynthesis of a New 18F-Labeled Thiol Reactive Prosthetic Group and Its Conjugate for Insulinoma Imaging

  2014cited by this paper
• A general copper-mediated nucleophilic 18F fluorination of arenes.

  2014cited by this paper
• Synthesis and biological evaluation of both enantiomers of [(18)F]flubatine, promising radiotracers with fast kinetics for the imaging of α4β2-nicotinic acetylcholine receptors.

  2014cited by this paper
• 2-Bromo-6-[(18) F]fluoropyridine: two-step fluorine-18 radiolabelling via transition metal-mediated chemistry.

  2014cited by this paper
• Imaging Evaluation of 5HT2C Agonists, [11C]WAY-163909 and [11C]Vabicaserin, Formed by Pictet–Spengler Cyclization

  2014cited by this paper
• Synthesis, Radiolabeling, and In Vivo Pharmacokinetic Evaluation of the Amyloid Beta Radioligand [11C]AZD4694 in Nonhuman Primates

  2014cited by this paper
• A universal procedure for the [¹⁸F]trifluoromethylation of aryl iodides and aryl boronic acids with highly improved specific activity.

  2014cited by this paper
• Radiosynthesis and ex vivo evaluation of [(11)C-carbonyl]carbamate- and urea-based monoacylglycerol lipase inhibitors.

  2014cited by this paper
• Microfluidic continuous-flow radiosynthesis of [18F]FPEB suitable for human PET imaging.

  2014cited by this paper
• Enantioselective radiosynthesis of positron emission tomography (PET) tracers containing [¹⁸F]fluorohydrins.

  2014cited by this paper
• Synthesis and labeling of a piperazine-based library of ¹¹C-labeled ligands for imaging of the vesicular acetylcholine transporter.

  2014cited by this paper
• Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

  2014cited by this paper

• Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP

  2024cites this paper
• Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP

  2023cites this paper
• Carbon-11 patents (2012–2022): synthetic methodologies and novel radiotracers for PET imaging

  2022cites this paper
• Radiolabeling with [11C]HCN for Positron emission tomography.

  2021cites this paper
• Syntheses of [11C]2- and [11C]3-trifluoromethyl-4-aminopyridine: potential PET radioligands for demyelinating diseases.

  2020cites this paper