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.
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 language | English |
|---|---|
| Pages (from-to) | 1395-1400 |
| Number of pages | 6 |
| Journal | Applied Radiation and Isotopes |
| Volume | 69 |
| Issue number | 10 |
| Early online date | 11 May 2011 |
| DOIs | |
| Publication status | Published - Oct 2011 |
Keywords
- 18F
- PET
- Neutravidin™
- breast cancer cells
- Biotin
Access to Document
- Biotin[18F]-Neutravidin
NOTICE: this is the author’s version of a work that was accepted for publication in Applied Radiation and Isotopes. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Applied Radiation and Isotopes, [VOL 69, ISSUE 10, (2011)] DOI: 10.1016/j.apradiso.2011.05.005