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

doi:10.1016/j.apradiso.2011.05.005

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 journal › Article

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 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	https://doi.org/10.1016/j.apradiso.2011.05.005
Publication status	Published - Oct 2011

Keywords

18F
PET
Neutravidin™
breast cancer cells
Biotin

Access to Document

10.1016/j.apradiso.2011.05.005

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
Submitted manuscript, 203 KB

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Smith, T. A. D., Simpson, M., Cheyne, R. W., & Trembleau, L. A. C. (2011). 18F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding to NeutravidinTM -trastuzumab pre-treated cells. Applied Radiation and Isotopes, 69(10), 1395-1400. https://doi.org/10.1016/j.apradiso.2011.05.005

18F-PEG-biotin : Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding to NeutravidinTM -trastuzumab pre-treated cells. / Smith, Timothy Andrew Davies; Simpson, Michael; Cheyne, Richard William; Trembleau, Laurent Alain Claude.

In: Applied Radiation and Isotopes, Vol. 69, No. 10, 10.2011, p. 1395-1400.

Research output: Contribution to journal › Article

@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{\texttrademark}–biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin{\texttrademark}-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{\texttrademark}-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{\texttrademark}-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{\texttrademark}–antibody conjugates. Highlights ¿ Boroaryl-biotin precursor is prepared. ¿ Rapid 18F-fluorination is demonstrated. ¿ HER-2 expressing breast cancer cells pre-treated with trastuzumab–Neutravidin{\texttrademark}. ¿ 18F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression. ",

keywords = "18F, PET , Neutravidin{\texttrademark}, breast cancer cells , Biotin",

author = "Smith, {Timothy Andrew Davies} and Michael Simpson and Cheyne, {Richard William} and Trembleau, {Laurent Alain Claude}",

year = "2011",

month = oct,

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 -