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: Recherche - Revue par des pairsArticle

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.

langueAnglais
Pages415-423
Nombre de pages9
journalNuclear Medicine and Biology
Volume43
Numéro7
Les DOIs
étatPublié - 2016

Empreinte digitale

Anti-Idiotypic Antibodies
Neoplasms
Single Photon Emission Computed Tomography Computed Tomography
Endoglin
Antibodies
Therapeutics
Endothelium
Patient Care
Thyroid Gland
Peptides
Bevacizumab
In Vitro Techniques
chloramine-T

mots-clés

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    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 Levêque and Caroline Bouzin and Anne Bol and Marc Dieu and Stephan Walrand and {Vander Borght}, Thierry and Olivier Feron and Vincent Grégoire and Davide Bonifazi and Carine Michiels and Stéphane Lucas and Bernard Gallez",
    year = "2016",
    doi = "10.1016/j.nucmedbio.2016.03.007",
    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: Recherche - Revue par des pairsArticle

    TY - JOUR

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

    T2 - Nuclear Medicine and Biology

    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

    VL - 43

    SP - 415

    EP - 423

    JO - Nuclear Medicine and Biology

    JF - Nuclear Medicine and Biology

    SN - 0969-8051

    IS - 7

    ER -