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.

肠纤维化是炎症性肠病的常见并发症，但仍难以检测。基质金属蛋白酶（MMP）在纤维化中起关键作用，因此是纤维化检测的潜在目标。我们确定针对MMPs的F（ab'）₂抗体片段的immunoPET是否检测到结肠炎引起的结肠纤维化。给小鼠施用2％硫酸葡聚糖硫酸钠处理的水1个周期（发炎）或3个周期（纤维化），或未治疗（对照）。通过多重/ ELISA分析结肠和肾胶原，先天细胞因子，MMP和粪便MPO浓度。工程改造了α-pro-MMP-9F（ab'）₂片段并与⁸⁹Zr用于PET成像，离体Cherenkov分析和生物分布。在发炎的小鼠中结肠固有的细胞因子浓度和粪便髓过氧化物酶升高，但在纤维化小鼠中没有升高，而胶原蛋白浓度在纤维化小鼠中升高。MMPs在发炎的小鼠中增加，但是在纤维化小鼠中只有pro-MMP-9保持增加。⁸⁹ Zr-pro-MMP-9 F（ab'）₂在肠内和纤维化小鼠的肾脏中摄取均增加，其中胶原蛋白和pro-MMP-9浓度升高。⁸⁹ Zr-pro-MMP-9 F（ab'）₂检测到结肠炎引起的肠纤维化及相关的肾纤维化。