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)

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

Fingerprint

biotin
Labeling
Polyethylene glycols
marking
Cells
synthesis
cells
multiple docking adapters
Fluorination
fluorination
nuclides
antibodies
Antibodies
Isotopes
aqueous solutions
Imaging techniques
Biotin
breast
blood
attachment

Keywords

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

Cite this

@article{410fa3fccc46460c9b34602ec1c47491,
title = "18F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding to NeutravidinTM -trastuzumab pre-treated cells",
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.",
keywords = "18F, PET , Neutravidin™, breast cancer cells , Biotin",
author = "Smith, {Timothy Andrew Davies} and Michael Simpson and Cheyne, {Richard William} and Trembleau, {Laurent Alain Claude}",
year = "2011",
month = "10",
doi = "10.1016/j.apradiso.2011.05.005",
language = "English",
volume = "69",
pages = "1395--1400",
journal = "Applied Radiation and Isotopes",
issn = "0969-8043",
publisher = "Elsevier Limited",
number = "10",

}

TY - JOUR

T1 - 18F-PEG-biotin

T2 - Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding to NeutravidinTM -trastuzumab pre-treated cells

AU - Smith, Timothy Andrew Davies

AU - Simpson, Michael

AU - Cheyne, Richard William

AU - Trembleau, Laurent Alain Claude

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

KW - 18F

KW - PET

KW - Neutravidin™

KW - breast cancer cells

KW - Biotin

U2 - 10.1016/j.apradiso.2011.05.005

DO - 10.1016/j.apradiso.2011.05.005

M3 - Article

VL - 69

SP - 1395

EP - 1400

JO - Applied Radiation and Isotopes

JF - Applied Radiation and Isotopes

SN - 0969-8043

IS - 10

ER -