Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer

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Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer. / Xavier, Catarina; Vaneycken, Ilse; D'huyvetter, Matthias; Heemskerk, Johannes; Keyaerts, Marleen; Vincke, Cécile; Devoogdt, Nick; Muyldermans, Serge; Lahoutte, Tony; Caveliers, Vicky; Aerts, An (Peer reviewer); Impens, Nathalie (Peer reviewer); Baatout, Sarah (Peer reviewer).

In: Journal of Nuclear Medicine, Vol. 54, No. 5, 13.05.2013, p. 776-784.

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Xavier, C, Vaneycken, I, D'huyvetter, M, Heemskerk, J, Keyaerts, M, Vincke, C, Devoogdt, N, Muyldermans, S, Lahoutte, T, Caveliers, V, Aerts, A, Impens, N & Baatout, S 2013, 'Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer', Journal of Nuclear Medicine, vol. 54, no. 5, pp. 776-784. https://doi.org/10.2967/jnumed.112.111021

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Xavier, Catarina ; Vaneycken, Ilse ; D'huyvetter, Matthias ; Heemskerk, Johannes ; Keyaerts, Marleen ; Vincke, Cécile ; Devoogdt, Nick ; Muyldermans, Serge ; Lahoutte, Tony ; Caveliers, Vicky ; Aerts, An ; Impens, Nathalie ; Baatout, Sarah. / Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer. In: Journal of Nuclear Medicine. 2013 ; Vol. 54, No. 5. pp. 776-784.

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@article{6d91004bf9cb4d0fb79c79a33c4bec83,
title = "Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer",
abstract = "Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti–human epidermal growth factor receptor type 2 (HER2) Nanobody with 68Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7- triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA- 2Rs15d was performed on healthy mice up to a dose of 10 mg/kg.",
keywords = "HER2, breast cancer, nanobody, iPET",
author = "Catarina Xavier and Ilse Vaneycken and Matthias D'huyvetter and Johannes Heemskerk and Marleen Keyaerts and C{\'e}cile Vincke and Nick Devoogdt and Serge Muyldermans and Tony Lahoutte and Vicky Caveliers and An Aerts and Nathalie Impens and Sarah Baatout",
note = "Score=10",
year = "2013",
month = "5",
day = "13",
doi = "10.2967/jnumed.112.111021",
language = "English",
volume = "54",
pages = "776--784",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "SNMMI - Society of Nuclear Medicine and Molecular Imaging",
number = "5",

}

RIS - Download

TY - JOUR

T1 - Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer

AU - Xavier, Catarina

AU - Vaneycken, Ilse

AU - D'huyvetter, Matthias

AU - Heemskerk, Johannes

AU - Keyaerts, Marleen

AU - Vincke, Cécile

AU - Devoogdt, Nick

AU - Muyldermans, Serge

AU - Lahoutte, Tony

AU - Caveliers, Vicky

A2 - Aerts, An

A2 - Impens, Nathalie

A2 - Baatout, Sarah

N1 - Score=10

PY - 2013/5/13

Y1 - 2013/5/13

N2 - Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti–human epidermal growth factor receptor type 2 (HER2) Nanobody with 68Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7- triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA- 2Rs15d was performed on healthy mice up to a dose of 10 mg/kg.

AB - Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti–human epidermal growth factor receptor type 2 (HER2) Nanobody with 68Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7- triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA- 2Rs15d was performed on healthy mice up to a dose of 10 mg/kg.

KW - HER2

KW - breast cancer

KW - nanobody

KW - iPET

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_128827

UR - http://knowledgecentre.sckcen.be/so2/bibref/10210

U2 - 10.2967/jnumed.112.111021

DO - 10.2967/jnumed.112.111021

M3 - Article

VL - 54

SP - 776

EP - 784

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 5

ER -

ID: 258653