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

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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.

Original languageEnglish
Pages (from-to)415-423
Number of pages9
JournalNuclear Medicine and Biology
Volume43
Issue number7
DOIs
Publication statusPublished - 2016

Keywords

  • Anti-endoglin antibody
  • CD105
  • Deiodination
  • KRYRR
  • SPECT/CT
  • Tumor

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