Skip to main content
SpringerLink
Log in

The Influence of Polysorbate 80 on the Radiochemical Synthesis of a PET Tracer in the FASTlab

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

The aim of current study was to investigate the influence of a common non-ionic surfactant, polysorbate 80 (PS80), on radioactive labelling process of a novel PET tracer, [18F]Flutemetamol.

Methods

Ferrous oxidation-xylenol orange (FOX) assay, in addition to UV/VIS and 1H NMR spectroscopies were applied to characterise the composition of the PS80 solution after storage. Multivariate Curve Resolution (MCR) and PLS analysis was used to establish correlation between quality of the PS80 solution and the RCP obtained after labelling.

Results

The levels of unsaturated fatty acid moieties of PS80 were negatively correlated to RCP of [18F]Flutemetamol after synthesis. This explains the slight increase in RCP when stored PS80 solutions were applied in the synthesis. The mechanism behind this observation is suggested to be related to radiation induced radical formation in the unsaturated fatty acids, which subsequently causes instability of the PET tracer. UV/VIS spectroscopy was demonstrated to have the ability as a possible control tool for quality assurance of the studied radioactive labelling process.

Conclusions

The presence of unsaturated fatty acid moieties in PS80 was found to be one of the most important factors responsible for the reduction in RCP of [18F]Flutemetamol after synthesis.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

MCR:

Mulitivariate curve resolution

PET:

Positron emission tomography

PLS:

Partial least squares

PS80:

Polysorbate 80

RCP:

Radiochemical purity

References

  1. Sartor Oand Venugopal D. Radiopharmaceuticals. In: Figg WD, Chau CH, Small EJ, editors. Drug management of prostate cancer. New York: Springer; 2010. p. 255–66.

    Chapter  Google Scholar 

  2. Adam MJ, Wilbur DS. Radiohalogens for imaging and therapy. Chem Soc Rev. 2005;34(2):153–63.

    Article  CAS  PubMed  Google Scholar 

  3. Mountz JM, Alavi A, Mountz JD. Emerging optical and nuclear medicine imaging methods in rheumatoid arthritis. Nat Rev Rheumatol. 2012;8(12):719–28.

    Article  CAS  PubMed  Google Scholar 

  4. Hannestad J. The application of PET imaging in psychoneuroimmunology research. In: Yan Q, editor. Psychoneuroimmunology, Vol. 934. New York: Humana Press; 2012. p. 325–53.

    Chapter  Google Scholar 

  5. Sasser TA, Van Avermaete AE, White A, Chapman S, Johnson JR, Van Avermaete T, et al. Bacterial infection probes and imaging strategies in clinical nuclear medicine and preclinical molecular imaging. Curr Top Med Chem. 2013;13(4):479-87.

  6. Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-pet for imaging β-amyloid pathology. JAMA. 2011;305(3):275–83.

    Article  CAS  PubMed  Google Scholar 

  7. Barthel H, Gertz H-J, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.

    Article  CAS  PubMed  Google Scholar 

  8. Nelissen N, Van Laere K, Thurfjell L, Owenius R, Vandenbulcke M, Koole M, et al. Phase 1 study of the Pittsburgh compound B derivative18F- flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med. 2009;50(8):1251–9.

    Article  CAS  PubMed  Google Scholar 

  9. Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment a phase 2 trial. Ann Neurol. 2010;68(3):319–29.

    Article  PubMed  Google Scholar 

  10. Hatashita S, Yamasaki H, Suzuki Y, Tanaka K, Wakebe D, Hayakawa H. [18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2014;41(2):290-300.

  11. Leinonen V, Rinne JO, Virtanen KA, Eskola O, Rummukainen J, Huttunen J, et al. Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients. Eur J Neurol. 2013;20(7):1043–52.

    Article  CAS  PubMed  Google Scholar 

  12. Thurfjell L, Lotjonen J, Lundqvist R, Koikkalainen J, Soininen H, Waldemar G, et al. Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment. Neuro-Degener Dis. 2012;10(1–4):246–9.

    Article  CAS  Google Scholar 

  13. Thonon D, Goblet D, Goukens E, Kaisin G, Paris J, Aerts J, et al. Fully automated preparation and conjugation of N-succinimidyl 4-[18F]Fluorobenzoate ([18F]SFB) with RGD peptide using a GE FASTlab™ synthesizer. Mol Imaging Biol. 2011;13(6):1088–95.

    Article  PubMed  Google Scholar 

  14. Swahn B-M, Sandell J, Pyring D, Bergh M, Jeppsson F, Juréus A, et al. Synthesis and evaluation of pyridylbenzofuran, pyridylbenzothiazole and pyridylbenzoxazole derivatives as 18F-PET imaging agents for β-amyloid plaques. Bioorg Med Chem Lett. 2012;22(13):4332–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hvattum E, Yip WL, Grace D, Dyrstad K. Characterization of polysorbate 80 with liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy: specific determination of oxidation products of thermally oxidized polysorbate 80. J Pharm Biomed Anal. 2012;62:7–16.

    Article  CAS  PubMed  Google Scholar 

  16. Wolff SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods in Enzymology, Vol. Volume 233. London: Academic; 1994. p. 182–9.

    Google Scholar 

  17. Smallcombe SH, Patt SL, Keifer PA. WET solvent suppression and its applications to LC NMR and high-resolution NMR spectroscopy. J Magn Reson Ser A. 1995;117(2):295–303.

    Article  CAS  Google Scholar 

  18. Ha E, Wang W, Wang YJ. Peroxide formation in polysorbate 80 and protein stability. J Pharm Sci. 2002;91(10):2252–64.

    Article  CAS  PubMed  Google Scholar 

  19. Kishore RSK, Pappenberger A, Dauphin IB, Ross A, Buergi B, Staempfli A, et al. Degradation of polysorbates 20 and 80: studies on thermal autoxidation and hydrolysis. J Pharm Sci. 2011;100(2):721–31.

    Article  CAS  PubMed  Google Scholar 

  20. Donbrow M, Azaz E, Pillersdorf A. Autoxidation of polysorbates. J Pharm Sci. 1978;67(12):1676–81.

    Article  CAS  PubMed  Google Scholar 

  21. Sehat N, Yurawecz M, Roach JG, Mossoba M, Kramer JG, Ku Y. Silver-ion high-performance liquid chromatographic separation and identification of conjugated linoleic acid isomers. Lipids. 1998;33(2):217–21.

    Article  CAS  PubMed  Google Scholar 

  22. Kishore R, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler H-C. The degradation of polysorbates 20 and 80 and its potential impact on the stability of biotherapeutics. Pharm Res. 2011;28(5):1194–210.

    Article  CAS  PubMed  Google Scholar 

  23. Hjelstuen OK, Svadberg A, Olberg DE, Rosser M. Standardization of fluorine-18 manufacturing processes: new scientific challenges for PET. Eur J Pharm Biopharm. 2011;78(3):307–13.

    Article  CAS  PubMed  Google Scholar 

  24. Yao J, Dokuru DK, Noestheden M, Park SS, Kerwin BA, Jona J, et al. A quantitative kinetic study of polysorbate autoxidation: the role of unsaturated fatty acid ester substituents. Pharm Res. 2009;26(10):2303–13.

    Article  CAS  PubMed  Google Scholar 

  25. Herman A, Boone T, Lu H. Characterization, formulation, and stability of Neupogen® (Filgrastim), a recombinant human granulocyte-colony stimulating factor. In: Pearlman Rand Wang YJ, editor. Formulation, characterization, and stability of protein drugs: case histories, Vol. 9. US: Springer; 2002. p. 303–28.

    Chapter  Google Scholar 

  26. Kerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci. 2008;97(8):2924–35.

    Article  CAS  PubMed  Google Scholar 

  27. Peter Wuelfing W, Kosuda K, Templeton AC, Harman A, Mowery MD, Reed RA. Polysorbate 80 UV/vis spectral and chromatographic characteristics - defining boundary conditions for use of the surfactant in dissolution analysis. J Pharm Biomed Anal. 2006;41(3):774–82.

    Article  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Ingrid Henriksen, Erlend Hvattum, Wenche Nordby and Arnfinn Andersen for scientific discussion. Svein Kvåle, Thanushan Rajanayagam, Lone Omtvedt and Grete Madsen for laboratory assistance.

Author information

Authors and Affiliations

  1. School of Pharmacy, Department of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316, Oslo, Norway

    Wai Lam Yip & Sverre Arne Sande

  2. GE Healthcare, Life Sciences, P.O. Box 4220, 0401, Oslo, Norway

    David Grace & Dirk Jan in’t Veld

  3. Phoenix Solutions AS, Solborgveien 17, 1528, Moss, Norway

    Per Christian Sontum

  4. Norwegian Medical Cyclotron Center AS, Sognsvannsveien 20, 0372, Oslo, Norway

    Tina Solvang

  5. KD Metrix, Spireaveien 10A, 0580, Oslo, Norway

    Knut Dyrstad

Authors
  1. Wai Lam Yip
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sverre Arne Sande
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Grace
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dirk Jan in’t Veld
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Per Christian Sontum
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tina Solvang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Knut Dyrstad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wai Lam Yip.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yip, W.L., Sande, S.A., Grace, D. et al. The Influence of Polysorbate 80 on the Radiochemical Synthesis of a PET Tracer in the FASTlab. Pharm Res 32, 1425–1437 (2015). https://doi.org/10.1007/s11095-014-1547-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-014-1547-4

KEY WORDS

Search

Navigation