Radioimmune Imaging of alfa4beta7 Integrin and TNFalfa for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease Articles uri icon

authors

  • SIGNORE, ALBERTO
  • BONFIGLIO, RITA
  • VARANI, MICHELA
  • GALLI, FILIPPO
  • CAMPAGNA, GIUSEPPE
  • DESCO MENENDEZ, MANUEL
  • CUSSO MULA, LORENA
  • MATTEI, MAURIZIO
  • WUNDER, ANDREAS
  • BORRI, FILIPPO
  • LUPO, MARIA T.
  • BONANNO, ELENA

publication date

  • March 2023

start page

  • 1

end page

  • 15

issue

  • 3

volume

  • 15

International Standard Serial Number (ISSN)

  • 1999-4923

abstract

  • Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-a4B7 integrin or radiolabelled anti-TNFa mAb could predict therapeutic outcome with unlabelled anti-a4B7 integrin or anti-TNFa mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-a4B7 integrin and anti-TNFa mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-a4B7 integrin or anti-TNFa mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled a4B7 integrin and anti-TNFa showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high a4B7 integrin or TNFa expression will benefit of therapy with unlabelled mAb.

subjects

  • Biology and Biomedicine
  • Medicine
  • Pharmacy

keywords

  • inflammatory bowel disease; dss-mouse model; tnf-a; a4b7 integrin; imaging inflammation