Year-end Sale % OFF 
Abstract
Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.
Highlights
Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect
We conducted the first immunoPET study of fibrosis to demonstrate that 89Zr labelled F(ab′)[2] antibody fragments directed against pro-Matrix metalloproteases (MMPs)-9 reliably detects colonic fibrosis in the absence of inflammation
Patients remains controversial; MMP-2, -3, -9 and tissue inhibitors of matrix metalloproteinases (TIMPs)-1 are reportedly increased to a similar extent in fibrotic and inflamed intestinal tissue relative to tissue from healthy subjects[14,15], while others observed that TIMP-1 is increased but MMP-3 is reduced in intestinal fibrosis relative to nearby unstrictured tissue[13]
Summary
Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. We determined whether immunoPET of F(ab′)[2] antibody fragments targeting MMPs detects colitis induced colonic fibrosis. MMP-2, -3, -8 and -9, and TIMP-1 are altered to varying extents in fibrotic tissue resected from IBD patients and in pre-clinical models of intestinal fibrosis[10,11,13,14,15]. ImmunoPET combines the superior target selectivity provided by antibodies with the sensitivity of PET and we, amongst others, have previously demonstrated that immunoPET strategies effectively detect intestinal inflammation[16,19,20,21]. Imaging and Therapy Research Unit (MITRU), South Australian Health and Medical Research Institute, Adelaide, Australia. 3Preclinical, Imaging and Research Laboratories (PIRL), South Australian Health and Medical Research
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
