Microfluidic radiolabeling of biomolecules with PET radiometals

Dexing Zeng, Amit V. Desai, David Ranganathan, Tobias D. Wheeler, Paul J.A. Kenis, David E. Reichert

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Introduction: A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. Methods: The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64Cu and 68Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Results: Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64Cu/68Ga using the microreactor, which demonstrates the ability to label both small and large molecules. Conclusions: A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.

Original languageEnglish (US)
Pages (from-to)42-51
Number of pages10
JournalNuclear Medicine and Biology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Microfluidics
Bovine Serum Albumin
Hot Temperature
Technology
Peptides
Temperature
Acids
Proteins
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Keywords

  • Cu
  • Ga
  • Microfluidic
  • PET
  • RGD

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Zeng, D., Desai, A. V., Ranganathan, D., Wheeler, T. D., Kenis, P. J. A., & Reichert, D. E. (2013). Microfluidic radiolabeling of biomolecules with PET radiometals. Nuclear Medicine and Biology, 40(1), 42-51. https://doi.org/10.1016/j.nucmedbio.2012.08.012

Microfluidic radiolabeling of biomolecules with PET radiometals. / Zeng, Dexing; Desai, Amit V.; Ranganathan, David; Wheeler, Tobias D.; Kenis, Paul J.A.; Reichert, David E.

In: Nuclear Medicine and Biology, Vol. 40, No. 1, 01.01.2013, p. 42-51.

Research output: Contribution to journalArticle

Zeng, D, Desai, AV, Ranganathan, D, Wheeler, TD, Kenis, PJA & Reichert, DE 2013, 'Microfluidic radiolabeling of biomolecules with PET radiometals', Nuclear Medicine and Biology, vol. 40, no. 1, pp. 42-51. https://doi.org/10.1016/j.nucmedbio.2012.08.012
Zeng, Dexing ; Desai, Amit V. ; Ranganathan, David ; Wheeler, Tobias D. ; Kenis, Paul J.A. ; Reichert, David E. / Microfluidic radiolabeling of biomolecules with PET radiometals. In: Nuclear Medicine and Biology. 2013 ; Vol. 40, No. 1. pp. 42-51.
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abstract = "Introduction: A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. Methods: The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64Cu and 68Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Results: Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90{\%} radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64Cu/68Ga using the microreactor, which demonstrates the ability to label both small and large molecules. Conclusions: A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.",
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