Gas Phase Transformations in Carbon-11 Chemistry - PubMed (original) (raw)

Review

Gas Phase Transformations in Carbon-11 Chemistry

Shuiyu Lu et al. Int J Mol Sci. 2024.

Abstract

The short-lived positron-emitter carbon-11 (_t_1/2 = 20.4 min; β+, 99.8%) is prominent for labeling tracers for use in biomedical research with positron emission tomography (PET). Carbon-11 is produced for this purpose with a cyclotron, nowadays almost exclusively by the 14N(p,α)11C nuclear reaction, either on nitrogen containing a low concentration of oxygen (0.1-0.5%) or hydrogen (~5%) to produce [11C]carbon dioxide or [11C]methane, respectively. These primary radioactive products can be produced in high yields and with high molar activities. However, only [11C]carbon dioxide has some utility for directly labeling PET tracers. Primary products are required to be converted rapidly and efficiently into secondary labeling synthons to provide versatile radiochemistry for labeling diverse tracer chemotypes at molecular positions of choice. This review surveys known gas phase transformations of carbon-11 and summarizes the important roles that many of these transformations now play for producing a broad range of labeling synthons in carbon-11 chemistry.

Keywords: PET; carbon-11; catalysts; gas phase; on-line processes; radiochemistry; radiotracer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Scheme 1

Decay of carbon-11 (A) and principle of PET (B). Reprinted and modified from Li and Conti, 2010 [3], with permission from Elsevier.

Scheme 2

Processes leading to [11C]carbon dioxide and [11C]methane by proton irradiation of nitrogen gas with low level oxygen (A) or ~5% hydrogen (B), respectively. * Indicates hot atom or energetic species.

Scheme 3

Conversions of [11C]carbon dioxide into other 11C-labeling agents: (A) [11C]methane; (B) [11C]carbon monoxide; (C) [11C]hydrogen cyanide; and (D) [11C]carbon disulfide.

Scheme 4

Conversion of [11C]methane into (A) [11C]carbon dioxide; (B) [11C]methanol; (C) [11C]hydrogen cyanide; and (D) [11C]acetylene.

Scheme 5

Halogenations of [11C]methane to produce useful labeling synthons: (A) fluorination; (B) chlorination; (C) bromination; and (D) iodination.

Scheme 5

Halogenations of [11C]methane to produce useful labeling synthons: (A) fluorination; (B) chlorination; (C) bromination; and (D) iodination.

Scheme 6

Conversions of [11C]carbon monoxide into other labeling synthons and intermediates: (A) [11C]phosgene; (B) [11C]carbonyl difluoride; and (C) proposed for [11C]methanol.

Scheme 7

Conversions of [11C]methanol into (A) [11C]formaldehyde and (B) [11C]iodomethane.

Scheme 8

Conversion of [1-11C]ethanol into [1-11C]ethylene.

Scheme 9

Conversions of [11C]carbon tetrachloride into [11C]phosgene.

Scheme 10

Metathetical conversions of [11C]haloalkanes into useful labeling synthons by passage over heated silver(I) or sodium salts into (A,B) [11C]methyl triflate; (C) [11C]iodomethane; (D) [11C]nitroalkanes; (E) [11C]methanethiol; (F) [11C]mesyl chloride; and (G) [_methyl_-11C]methyl isocyanate.

Scheme 11

Conversions of [11C]iodomethane into (A) [11C]hydrogen cyanide and (B) [11C]carbon disulfide.

Scheme 12

Conversion of [11C]hydrogen cyanide into [11C]cyanogen bromide.

Scheme 13

Conversion of [1-11C]butyric acid into [1-11C]propylketene.

References

1. Phelps M.E. Positron emission tomography provides molecular imaging of biological processes. Proc. Natl. Acad. Sci. USA. 2000;97:9226–9233. doi: 10.1073/pnas.97.16.9226. - DOI - PMC - PubMed
1. Cherry S.R., Badawi R.D., Karp J.S., Moses W.W., Price P., Jones T. Total-body imaging: Transforming the role of positron emission tomography. Sci. Transl. Med. 2017;9:eaaf6169. doi: 10.1126/scitranslmed.aaf6169. - DOI - PMC - PubMed
1. Li Z., Conti P.S. Radiopharmaceutical chemistry for positron emission tomography. Adv. Drug Deliv. Rev. 2010;62:1031–1051. doi: 10.1016/j.addr.2010.09.007. - DOI - PubMed
1. Ferrieri R.A., Wolf A.P. The chemistry of positron emitting nucleogenic (hot) atoms with regard to preparation of labelled compounds of practical utility. Radiochim. Acta. 1983;34:69–84. doi: 10.1524/ract.1983.34.12.69. - DOI
1. Ferrieri R.A. Handbook of Radiopharmaceuticals—Radiochemistry and Applications. John Wiley & Sons; Hoboken, NJ, USA: 2002. Production and Application of Synthetic Precursors Labeled with Carbon-11 and Fluorine-18; pp. 229–282. - DOI

Gas Phase Transformations in Carbon-11 Chemistry - PubMed (original) (raw)