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Nucl Med Biol. 2016 Jul;43(7):415-23. doi: 10.1016/j.nucmedbio.2016.03.007. Epub 2016 Mar 29.

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

Author information

1
Biomedical Magnetic Resonance Research Group (REMA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium.
2
Pharmacology and Therapeutics Unit (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Mounier 53, 1200, Brussels, Belgium.
3
Centre for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
4
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
5
Namur Research College and Department of Chemistry (NARC), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
6
Research Centre for the Physics of Matter and Radiation (PMR), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
7
Biomedical Magnetic Resonance Research Group (REMA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium. Electronic address: Bernard.Gallez@uclouvain.be.

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 ((125)I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker ((125)I-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 24h for (125)I-anti-CD105-mAbs (91.9±4.0%ID/ml) versus(125)I-KRYRR-anti-CD105-mAbs (4.4±0.6%ID/ml). Tumor uptake of (125)I-anti-CD105-mAbs (0.9±0.3%ID/ml) was significantly lower than that of (125)I-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

PMID:
27179250
DOI:
10.1016/j.nucmedbio.2016.03.007
[Indexed for MEDLINE]

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