Immuno-PET Imaging of TNF-α in Colitis Using 89Zr-DFO-infliximab
Immuno-PET Imaging of TNF-α in Colitis Using 89Zr-DFO-infliximab
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DOI：
10.1021/acs.molpharmaceut.2c00411
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发表时间：
2022-08-29
影响因子：
4.9
通讯作者：
Yang, Min
中科院分区：
文献类型：
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作者：
Yan, Ge;Wang, Xinyu;Yang, Min
肿瘤坏死因子-α (TNF-α) 中和在炎症性肠病 (IBD) 的治疗中变得越来越重要。一系列单克隆抗体在临床上被批准用于抗TNF-α治疗。然而，对整个结肠的 TNF-α 水平进行全面评估仍然具有挑战性，这有助于 IBD 的诊断并预测抗 TNF-α 的疗效。在这里，我们用长寿命放射性核素 89Zr 放射性标记英夫利昔单抗，用于体内 TNF-α 的免疫正电子发射断层扫描 (PET) 成像。在葡聚糖硫酸钠诱导的结肠炎小鼠的炎症结肠中检测到TNF-α水平升高。 89Zr-去铁胺-英夫利昔单抗的免疫-PET 成像显示炎症结肠中的高摄取（7.1 & PLUSMN；0.3%ID/g），显着高于健康对照组和阻断组。结肠与肌肉的比值达到10以上，并在注射后10小时内维持在较高水平。离体生物分布研究也证实了炎症结肠中的优异吸收。这项研究提供了一种体内免疫 PET 方法来对促炎细胞因子 TNF-α 进行分子成像。它在 IBD 和其他自身免疫性疾病的诊断和预测疗效方面具有广阔的前景。
Tumor necrosis factor-alpha (TNF-alpha) neutraliza-tion has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-alpha therapy. However, a comprehensive assessment of TNF-alpha levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-alpha efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides 89Zr for immuno-positron emission tomography (PET) imaging of TNF-alpha in vivo. The increased TNF-alpha level was detected in the inflammatory colon of the dextran sodium sulfate-induced colitis mice. The immuno-PET imaging of 89Zr-desferrioxamine-infliximab reveals a high uptake (7.1 & PLUSMN; 0.3%ID/g) in the inflammatory colon, which is significantly higher than in the healthy control and blocked groups. The colon-to-muscle ratio reached more than 10 and was maintained at a high level for 10 h after injection. The ex vivo biodistribution study also verified the superior uptake in the inflammatory colon. This study provides an in vivo immune-PET approach to molecular imaging of the pro-inflammatory cytokine TNF-alpha. It is promising in diagnosing and predicting efficacy in both IBD and other autoimmune diseases.