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Oncotarget. 2017 Jul 27;8(49):85185-85202. doi: 10.18632/oncotarget.19616. eCollection 2017 Oct 17.

Radiolabelled polymeric IgA: from biodistribution to a new molecular imaging tool in colorectal cancer lung metastases.

Author information

1
Nuclear Medicine Department, Dupuytren University Hospital, 87042 Limoges, France.
2
EA 3842 - Cellular Homeostasis and Diseases, Faculty of Medicine, University of Limoges, 87025 Limoges, France.
3
B Cell Design SAS, 87000 Limoges, France.
4
UMR CNRS 7276 - CRIBL, University of Limoges, 87025 Limoges, France.

Abstract

By radiolabelling monomeric (m) and polymeric (p) IgA with technetium 99m (99mTc), this study assessed IgA biodistribution and tumour-targeting potency. IgA directed against carcinoembryonic antigen (CEA), a colorectal cancer marker, was selected to involve IgA mucosal tropism. Ig was radiolabelled with 99mTc-tricarbonyl after derivatisation by 2-iminothiolane. 99mTc-IgA was evaluated by in vitro analysis. The biodistributions of radiolabelled anti-CEA mIgA, pIgA and IgG were compared in normal mice. Anti-CEA pIgA tumour uptake was studied in mice bearing the WiDr caecal orthotopic graft. IgA radiolabelling was obtained with a high yield, was stable in PBS and murine plasma, and did not alter IgA binding functionality (Kd ≈ 25 nM). Biodistribution studies in normal mice confirmed that radiolabelled pIgA - and to a lesser extent, mIgA - showed strong and fast mucosal tropism and a shorter serum half-life than IgG. In caecal tumour model mice, evaluation of the anti-CEA-pIgA biodistribution showed a high uptake in lung metastases, confirmed by histological analysis. However, no radioactivity uptake increase in the tumoural caecum was discerned from normal intestinal tissue, probably due to high IgA caecal natural tropism. In microSPECT/CT imaging, 99mTc-IgA confirmed its diagnostic potency of tumour in mucosal tissue, even if detection threshold by in vivo imaging was higher than post mortem studies. Contribution of the FcαRI receptor, studied with transgenic mouse model (Tsg SCID-CD89), did not appear to be determinant in 99mTc-IgA uptake. Pre-clinical experiments highlighted significant differences between 99mTc-IgA and 99mTc-IgG biodistributions. Furthermore, tumoural model studies suggested potential targeting potency of pIgA in mucosal tissues.

KEYWORDS:

anti-CEA IgA; colorectal cancer imaging; metastases; mucosal biodistribution; radiolabelling

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no competing interests. B Cell Design Society provided support in the form of a salary for authors, A. Cuvillier and G. Champier, Ig production and molecular reagents and mice supply, but did not have any additional role in the study.

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