18F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding to NeutravidinTM -trastuzumab pre-treated cells

Timothy Andrew Davies Smith, Michael Simpson, Richard William Cheyne, Laurent Alain Claude Trembleau

Research output: Contribution to journalArticle

7 Citations (Scopus)
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Abstract

In terms of nuclear decay 18F is the most ideal PET nuclide but its short t1/2 precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin™–biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin™-conjugated antibodies.

Methods
Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with 18F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin™-conjugated trastuzumab, washed, and then incubated with 18F-PEG-biotin.

Results
The 18F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel 18F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin™-conjugated trastuzumab.

Conclusion
Biotin can be functionalised with boroaryl and readily 18F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin™–antibody conjugates.

Highlights
¿ Boroaryl-biotin precursor is prepared. ¿ Rapid 18F-fluorination is demonstrated. ¿ HER-2 expressing breast cancer cells pre-treated with trastuzumab–Neutravidin™. ¿ 18F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression.

Original languageEnglish
Pages (from-to)1395-1400
Number of pages6
JournalApplied Radiation and Isotopes
Volume69
Issue number10
Early online date11 May 2011
DOIs
Publication statusPublished - Oct 2011

Keywords

  • 18F
  • PET
  • Neutravidin™
  • breast cancer cells
  • Biotin

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