Biodistribution of 125I-labeled anti-endoglin antibody using SPECT/CT imaging: Impact of in vivo deiodination on tumor accumulation in mice

Linda Karmani, Philippe Levêque, Caroline Bouzin, Anne Bol, Marc Dieu, Stephan Walrand, Thierry Vander Borght, Olivier Feron, Vincent Grégoire, Davide Bonifazi, Carine Michiels, Stéphane Lucas, Bernard Gallez

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Introduction: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. Methods: Anti-CD105 mAbs were radioiodinated directly using chloramine-T (125I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker (125I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. Results: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24 h for 125I-anti-CD105-mAbs (91.9 ± 4.0%ID/ml) versus 125I-KRYRR-anti-CD105-mAbs (4.4 ± 0.6%ID/ml). Tumor uptake of 125I-anti-CD105-mAbs (0.9 ± 0.3%ID/ml) was significantly lower than that of 125I-KRYRR-anti-CD105-mAbs (4.7 ± 0.2%ID/ml). Conclusions: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. Advances in knowledge and implications for patient care: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.

langue originaleAnglais
Pages (de - à)415-423
Nombre de pages9
journalNuclear Medicine and Biology
Volume43
Numéro de publication7
Les DOIs
étatPublié - 2016

Empreinte digitale

Anti-Idiotypic Antibodies
Neoplasms
Antibodies
Single Photon Emission Computed Tomography Computed Tomography
Endoglin
Endothelium
Patient Care
Thyroid Gland
Therapeutics
Peptides

Citer ceci

@article{d4f5497525d44dbd9aa2beec68239675,
title = "Biodistribution of 125I-labeled anti-endoglin antibody using SPECT/CT imaging: Impact of in vivo deiodination on tumor accumulation in mice",
abstract = "Introduction: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. Methods: Anti-CD105 mAbs were radioiodinated directly using chloramine-T (125I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker (125I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. Results: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24 h for 125I-anti-CD105-mAbs (91.9 ± 4.0{\%}ID/ml) versus 125I-KRYRR-anti-CD105-mAbs (4.4 ± 0.6{\%}ID/ml). Tumor uptake of 125I-anti-CD105-mAbs (0.9 ± 0.3{\%}ID/ml) was significantly lower than that of 125I-KRYRR-anti-CD105-mAbs (4.7 ± 0.2{\%}ID/ml). Conclusions: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. Advances in knowledge and implications for patient care: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.",
keywords = "Anti-endoglin antibody, CD105, Deiodination, KRYRR, SPECT/CT, Tumor",
author = "Linda Karmani and Philippe Lev{\^e}que and Caroline Bouzin and Anne Bol and Marc Dieu and Stephan Walrand and {Vander Borght}, Thierry and Olivier Feron and Vincent Gr{\'e}goire and Davide Bonifazi and Carine Michiels and St{\'e}phane Lucas and Bernard Gallez",
year = "2016",
doi = "10.1016/j.nucmedbio.2016.03.007",
language = "English",
volume = "43",
pages = "415--423",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "7",

}

Biodistribution of 125I-labeled anti-endoglin antibody using SPECT/CT imaging : Impact of in vivo deiodination on tumor accumulation in mice. / Karmani, Linda; Levêque, Philippe; Bouzin, Caroline; Bol, Anne; Dieu, Marc; Walrand, Stephan; Vander Borght, Thierry; Feron, Olivier; Grégoire, Vincent; Bonifazi, Davide; Michiels, Carine; Lucas, Stéphane; Gallez, Bernard.

Dans: Nuclear Medicine and Biology, Vol 43, Numéro 7, 2016, p. 415-423.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Biodistribution of 125I-labeled anti-endoglin antibody using SPECT/CT imaging

T2 - Impact of in vivo deiodination on tumor accumulation in mice

AU - Karmani, Linda

AU - Levêque, Philippe

AU - Bouzin, Caroline

AU - Bol, Anne

AU - Dieu, Marc

AU - Walrand, Stephan

AU - Vander Borght, Thierry

AU - Feron, Olivier

AU - Grégoire, Vincent

AU - Bonifazi, Davide

AU - Michiels, Carine

AU - Lucas, Stéphane

AU - Gallez, Bernard

PY - 2016

Y1 - 2016

N2 - Introduction: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. Methods: Anti-CD105 mAbs were radioiodinated directly using chloramine-T (125I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker (125I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. Results: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24 h for 125I-anti-CD105-mAbs (91.9 ± 4.0%ID/ml) versus 125I-KRYRR-anti-CD105-mAbs (4.4 ± 0.6%ID/ml). Tumor uptake of 125I-anti-CD105-mAbs (0.9 ± 0.3%ID/ml) was significantly lower than that of 125I-KRYRR-anti-CD105-mAbs (4.7 ± 0.2%ID/ml). Conclusions: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. Advances in knowledge and implications for patient care: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.

AB - Introduction: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. Methods: Anti-CD105 mAbs were radioiodinated directly using chloramine-T (125I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker (125I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. Results: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24 h for 125I-anti-CD105-mAbs (91.9 ± 4.0%ID/ml) versus 125I-KRYRR-anti-CD105-mAbs (4.4 ± 0.6%ID/ml). Tumor uptake of 125I-anti-CD105-mAbs (0.9 ± 0.3%ID/ml) was significantly lower than that of 125I-KRYRR-anti-CD105-mAbs (4.7 ± 0.2%ID/ml). Conclusions: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. Advances in knowledge and implications for patient care: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.

KW - Anti-endoglin antibody

KW - CD105

KW - Deiodination

KW - KRYRR

KW - SPECT/CT

KW - Tumor

UR - http://www.scopus.com/inward/record.url?scp=84966331174&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2016.03.007

DO - 10.1016/j.nucmedbio.2016.03.007

M3 - Article

AN - SCOPUS:84966331174

VL - 43

SP - 415

EP - 423

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 7

ER -