Skip to main content

Advertisement

SpringerLink
Log in

Current perspectives of 14C-isotope measurement in biomedical accelerator mass spectrometry

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Accelerator mass spectrometry (AMS) is an extremely sensitive nuclear physics technique developed in the mid-70’s for radiocarbon dating of historical artefacts. The technique centres round the use of a tandem Van de Graaff accelerator to generate the potential energy to permit separation of elemental isotopes at the single atom level. AMS was first used in the early 90’s for the analysis of biological samples containing enriched 14C for toxicology and cancer research. Since that time biomedical AMS has been used in the study of (1) metabolism of xenobiotics in animals and humans (2) pathways of drug metabolism (3) biomarkers (4) metabolism of endogenous molecules including vitamins (5) DNA and protein binding studies and (6) clinical diagnosis. A new drug development concept which relies on the ultrasensitivity of AMS known as human microdosing (Phase 0) is being used to obtain early human metabolism information of candidate drugs arising out of discovery. These various aspects of AMS are reviewed in this article and a perspective on future applications of AMS provided.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bennett CL, Beukens RP, Glover MR, Gove HE, Liebert RB, Litherland AE, Purser KH, Sondheim WE (1977) Science 198:508

    CAS  Google Scholar 

  2. Nelson DE, Korteling RG, Stott WR (1977) Science 198:507

    CAS  Google Scholar 

  3. Buchholz BA, Arjomand A, Dueker SR, Schneider PD, Clifford AJ, Vogel JS (1999) Anal Biochem 269:348–352

    PubMed  Google Scholar 

  4. L’Annunziata MF, Kessler MJ (1998) Radiotracer liquid scintillation analysis. In: L’Annunziata MF (ed) Handbook of radioactivity analysis. Academic Press, New York

  5. Vogel JS, Turteltaub KW, Finkel R (1995) Anal Chem 67:353A–359A

    PubMed  Google Scholar 

  6. Barker J, Garner RC (1999) Rapid Commun Mass Spectrom 13:285–293

    Article  PubMed  Google Scholar 

  7. Turteltaub KW, Vogel JS (2000) Curr Pharm Des 6:991–1007

    PubMed  Google Scholar 

  8. Lappin G, Garner RC (2003) Ultra-sensitive detection of radiolabelled drugs and their metabolites using accelerator mass spectrometry. In: Smith RM, Wilson ID (eds) Handbook of analytical separations. Elsevier, Amsterdam

  9. Turteltaub KW, Felton JS, Gledhill BL, Vogel JS, Southon JR, Caffee MW, Finkel RC, Nelson DE, Proctor ID, Davis JC (1990) Proc Natl Acad Sci USA 87:5288–5292

    PubMed  Google Scholar 

  10. Felton JS, Turteltaub KW (1994) Environ Health Perspect 102:450–452

    PubMed  Google Scholar 

  11. Lappin G, Garner RC (2003) Nat Rev (Drug Discovery) 2:233–240

    Google Scholar 

  12. Committee for Proprietary Medicinal Products (2003) Position paper on non-clinical safety studies to support clinical trials with a single microdose. CPMP/SWP/2599/02

  13. Vogel JS (1992) Radiocarbon 34:344–350

    Google Scholar 

  14. Mucciarone DA, Dunbar RB (1992) J Sed Petrol 62:731–733

    Google Scholar 

  15. Hotchkis M, Fink D, Tuniz C, Vogt S (2000) Appl Radiat Isot 53:31–37

    Article  PubMed  Google Scholar 

  16. International Commission on Radiological Protection in Biomedical Research (1992) ICRP Publication 62 Ann ICRP 22(3):1–18

    Google Scholar 

  17. Dolphin GW, Eve IS (1966) Health Phys 12:163–172

    PubMed  Google Scholar 

  18. Turteltaub KW, Vogel JS, Frantz CE, Shen N (1992) Cancer Res 52:4682–4687

    PubMed  Google Scholar 

  19. Frantz CE, Bangerter C, Fultz E, Mayer KM, Vogel JS, Turteltaub KW (1995) Carcinogenesis 16:367–373

    CAS  PubMed  Google Scholar 

  20. Turteltaub KW, Mauthe RJ, Dingley KH, Vogel JS, Frantz CE, Garner RC, Shen N (1997) Mutation Res 376:243–252

    Article  PubMed  Google Scholar 

  21. Mauthe RJ, Dingley KH, Leveson SH, Freeman PHT, Turesky RJ, Garner RC, Turteltaub KW (1999) Int J Cancer 80:539–545

    Article  PubMed  Google Scholar 

  22. Turteltaub KW, Dingley KH, Curtis KD, Malfatti MA, Turesky RJ, Garner RC, Felton JS, Lang NP (1999) Cancer Lett 143:149–155

    Article  PubMed  Google Scholar 

  23. Garner RC, Lightfoot TJ, Cupid BC, Russell D, Coxhead JM, Kutschera W, Priller A, Rom W, Steier P, Alexander DJ, Leveson SH, Dingley KH, Mauthe RJ, Turteltaub KW (1999) Cancer Lett 143:161–165

    Article  PubMed  Google Scholar 

  24. Lightfoot TJ, Coxhead JM, Cupid BC, Nicholson S, Garner RC (2000) Mutation Res 472:119–127

    Article  Google Scholar 

  25. Creek MR, Mani C, Vogel JS, Turteltaub KW (1997) Carcinogenesis 18:2421–2427

    CAS  PubMed  Google Scholar 

  26. Mani C, Freeman S, Nelson DO, Vogel JS, Turteltaub KW (1999) Toxicol Appl Pharmacol 159:83–90

    Article  PubMed  Google Scholar 

  27. Williams KE, Carver TA, Miranda JJL, Kautianen A, Vogel JS, Dingley K, Baldwin MA, Turteltaub KW, Burlingame AL (2002) Mol Cell Proteomics 1:885–895

    Article  PubMed  Google Scholar 

  28. Kwok ESC, Bucholz BA, Vogel JS, Turteltaub KW, Eastmond DA (1999) Toxicol Appl Pharmacol 159:18–24

    Article  PubMed  Google Scholar 

  29. White INH, Martin EA, Mauthe RJ, Vogel JS, Turteltaub KW, Smith LL (1997) Chem Biol Interact 106:149–160

    Article  PubMed  Google Scholar 

  30. Li XS, Wang HF, Shi JY, Wang XY, Liu YF, Li K, Lu XY, Wang JJ, Liu KX, Guo, Z Y (1996) Radiocarbon 38:347–353

    CAS  Google Scholar 

  31. Shi J, Wang H, Wu X, Li X, Liu Y, Li K, Lu X, Wang J, Liu K (1997) Chin Sci Bull 42:1662–1664

    CAS  Google Scholar 

  32. Kautiainen A, Vogel JS, Turteltaub KW (1997) Chem Biol Interact 106:109–121

    Article  PubMed  Google Scholar 

  33. Vogel JS, Turteltaub KW (1998) In: Müller C (ed) Mathematical modeling in experimental nutrition. Plenum, New York

  34. Stenström K, Leide-Svegborn S, Erlandsson B, Hellborg R, Mattsson S, Nilsson L-E, Nosslin B, Skog G, Wiebert A (1996) Appl Radiat Isot 47:4176–4220

    Google Scholar 

  35. Clifford AJ, Arjomand A, Dueker SR, Schneider PD, Buchholz BA, Vogel JS (1998) In: Müller C (ed) Mathematical modeling in experimental nutrition. Plenum, New York

  36. Dueker SR, Lin Y, Buchholz BA, Schneider PD, Lame MW, Segall HJ, Vogel JS, Clifford AJ (2000) J Lipid Res 41:1790–1800

    PubMed  Google Scholar 

  37. Svegborn SL, Stenström K, Olofsson M, Mattsson S, Nilsson L-E, Nosslin B, Pau K, Johansson L, Erlansson B, Hellborg R, Skog G (1999) Eur J Nucl Med 26:573–580

    Article  CAS  PubMed  Google Scholar 

  38. Gunnarsson M, Svegborn SL, Stenström K, Skog G, Nilsson L-E, Hellborg R, Mattsson S (2002) Br J Radiol 75:982–986

    PubMed  Google Scholar 

  39. Bortz JT, Wertz PW, Downing DT (1989) J Invest Dermatol 93:723–727

    PubMed  Google Scholar 

  40. Williams ML, Vogel JS, Ghadially R, Brown BE, Elia PM (1992) Arch Dermatol 128:1065–1071

    Article  PubMed  Google Scholar 

  41. Bogen KT, Keating GA, Meissner S, Vogel JS (1998) J Exposure Anal Environ Epidemiol 8:253–271

    CAS  Google Scholar 

  42. Gilman SD, Gee SJ, Hammock BD, Vogel JS, Haak K, Buchholz A, Freeman SPHT, Wester RC, Hui X, Maibach HI (1998) Anal Chem 70:3463–3469

    Article  PubMed  Google Scholar 

  43. Buchholz BA, Fultz E, Haack KW, Vogel JS, Gilman SD, Gee SG, Hammock BD, Hui X, Wester RC, Maibach HI (1999) Anal Chem 71:3519–3525

    Article  PubMed  Google Scholar 

  44. Buchholz BA, Pawley NH, Vogel JS, Mauthe RJ (1997) J Appl Toxicol 17:231–234

    Article  PubMed  Google Scholar 

  45. Garner RC, Barker J, Flavell C, Garner JV, Whattam M, Young GC, Cussans N, Jezequel S, Leong D (2000) J Pharm Biomed Anal 24:197–209

    Article  CAS  PubMed  Google Scholar 

  46. Garner RC, Leong D (2000) Nucl Instrum Methods Phys Res B 172:892–898

    Article  Google Scholar 

  47. Kaye B, Garner RC, Mauthe RJ, Freeman SPHT, Turteltaub KW (1997) J Pharm Biomed Anal 16:541–543

    Article  Google Scholar 

  48. Garner RC (2000) Current Drug Metab 1:205–213

    CAS  Google Scholar 

  49. Garner RC (2001) In: Pleiss U, Voges R (eds) Synthesis and applications of isotopically labelled compounds, vol 7. Wiley

  50. Garner RC (1999) European Pharmaceutical Contractor Technomark Consulting Services, November 1999, pp 22–28

  51. Cupid BC, Garner RC (1998) In: Gooderman N (ed) Drug metabolism: towards the next millennium. IOS Press

  52. Vogel JS, Turteltaub KW (1994) Nucl Instrum Methods Phys Res B 92:445–453

    Article  Google Scholar 

  53. Fifield LK (1999) Rep Prog Phys 62:1223–1274

    Article  Google Scholar 

  54. Young G, Ellis W, Ayrton J, Hussey E, Adamkiewicz B (2001) Xenobiotica 31:619–632

    Article  PubMed  Google Scholar 

  55. Garner RC, Garner JV, Gregory S, Whattam M, Calam A, Leong D (2002) J Pharm Sci 91:32–40

    Article  PubMed  Google Scholar 

  56. Garner RC, Goris I, Laenen AAE, Vanhoutte E, Meuldermans W, Gregory S, Garner JV, Leong D, Whattam Calam A, Snel CAW (2002) Drug Metab Dispos 30:823–830

    Article  Google Scholar 

  57. Dingley KH, Roberts ML, Velsko CA, Turteltaub KW (1998) Chem Res Toxicol 11:1217–1222

    Article  PubMed  Google Scholar 

  58. Faarinen M, Magnusson C-E, Hellborg R, Mattsson S, Kiisk M, Persson P, Schütz A, Skog G, Stenström K (2001) J Inorg Biochem 87:57–61

    Article  PubMed  Google Scholar 

  59. Synal H-A, Beer J, Bonani G, Lukasczyk Ch, Suter M (1994) Nucl Instrum Methods Phys Res B 92:79–84

    Article  Google Scholar 

  60. Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, di Tada ML, Liu K (1998) J Inorg Biochem 69:177–180

    Article  PubMed  Google Scholar 

  61. Zafar TA, Weaver CM, Martin BR, Flarend R, Elmore D (1997) Proc Soc Exp Biol Med 216:81–85

    CAS  PubMed  Google Scholar 

  62. Dittrich-Hannen B, Ames F, Suter M, Wagner MJM, Schnabel Ch, Michel R, Herpers U, Günther E (1996) Nucl Instrum Methods Phys Res B 113:453–456

    Article  Google Scholar 

  63. Bhattacharyya MH, Sacco-Gibson N, Peterson DP (1990) Nucl Instrum Methods Phys Res B 52:531–535

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Xceleron Ltd, York Biocentre, Innovation Way, York, YO10 5NY, UK

    Graham Lappin & R. Colin Garner

Authors
  1. Graham Lappin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Colin Garner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Colin Garner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lappin, G., Garner, R.C. Current perspectives of 14C-isotope measurement in biomedical accelerator mass spectrometry. Anal Bioanal Chem 378, 356–364 (2004). https://doi.org/10.1007/s00216-003-2348-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-003-2348-5

Keywords

Search

Navigation