99mTc-CXCL8 SPECT to Monitor Disease Activity in Inflammatory Bowel Disease
99mTc-CXCL8 SPECT to Monitor Disease Activity in Inflammatory Bowel Disease
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DOI：
10.2967/jnumed.115.165795
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发表时间：
2016-03-01
影响因子：
9.3
通讯作者：
Oyen, Wim J. G.
中科院分区：
文献类型：
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作者：
Aarntzen, Erik H. J. G.;Hermsen, Rick;Oyen, Wim J. G.
炎症性肠病（IBDs）被定义为慢性复发性免疫介导的胃肠道疾病。IBD恶化的特点是主要表达CXCL8受体的活化中性粒细胞进入肠壁，导致严重损伤。考虑到其慢性复发的特点，准确和及时的诊断是早期适应治疗和减轻疾病负担的关键。然而，内镜评估是侵入性的，并且与穿孔的风险增加有关。我们之前在临床前模型（包括结肠炎和临床研究）中开发了tc -99m标记的CXCL8制剂。方法：在这项研究中，我们研究了Tc-99m-CXCL8 SPECT在IBD患者中检测和定位疾病活动的准确性。30例患者（15例克罗恩病，15例溃疡性结肠炎），研究了92对组织学和（99m）TcCXCL8扫描。注射400 MBq Tc-99m-CXCL8后进行成像。注射后30min和4h分别获得腹部平面和SPECT图像。结果：Tc-99m-CXCL8扫描对活动性疾病的总体敏感性和特异性分别为95%和44%，内窥镜检查为71%和70%。Tc-99m-CXCL8的积累程度与受累粘膜中性粒细胞内流程度相关。从92个节段对计算得出的每个节段的敏感性和特异性分别为82%和72%，阴性预测值为81%，总体阳性预测值为74%。通过使用不同的截止值，可以以牺牲灵敏度为代价来增加特异性。在74个节段对中，内镜检查的总体敏感性和特异性分别为74%和85%，阳性预测值为81%，阴性预测值为79%。结论：Tc-99m-CXCL8 SPECT提供了一种新的成像技术，可以靶向中性粒细胞募集到肠壁，特别是在中度至重度IBD恶化中。进一步的验证研究有必要增强Tc-99m-CXCL8 SPECT作为生物标志物，以个性化的方式扩大或减少免疫调节药物的治疗。
Inflammatory bowel diseases (IBDs) are defined as chronic relapsing immune-mediated disorders of the gastrointestinal tract. IBD exacerbations are characterized by recruitment of mainly CXCL8 receptor-expressing activated neutrophils into the intestinal wall, leading to severe damage. Considering its chronic relapsing character, accurate and timely diagnosis of an exacerbation is pivotal for early adaptation of the treatment and reduction of the disease burden. However, endoscopic evaluation is invasive and associated with an increased risk of perforation. We previously developed a Tc-99m-labeled CXCL8 preparation in preclinical models including colitis and clinical studies. Methods: In this study, we investigate the accuracy of Tc-99m-CXCL8 SPECT to detect and localize disease activity in a prospective series of patients with IBD. Thirty patients (15 Crohns disease, 15 ulcerative colitis) participated, and 92 segmental pairs of histology and (99m)TcCXCL8 scans were studied. Imaging was performed after injection of 400 MBq of Tc-99m-CXCL8. Planar and SPECT images of the abdomen were acquired at 30 min and 4 h after the injection. Results: The overall sensitivity and specificity on a per-patient basis for the detection of active disease were 95% and 44% for Tc-99m-CXCL8 scan and 71% and 70% for endoscopy. The degree of Tc-99m-CXCL8 accumulation correlated to the degree of neutrophilic influx in affected mucosa. Sensitivity and specificity on a per-segment basis, calculated from the 92 segmental pairs, were 82% and 72%, negative predictive value was 81%, and overall positive predictive value was 74%. Specificity could be increased at the expense of sensitivity using different cutoffs. In 74 segmental pairs, overall sensitivity and specificity for endoscopy were 74% and 85%, positive predictive value was 81%, and negative predictive value was 79%. Conclusion: Tc-99m-CXCL8 SPECT provides a novel imaging technique to target neutrophil recruitment to the intestinal wall, especially in moderate to severe exacerbations of IBD. Further validation studies are warranted to potentiate Tc-99m-CXCL8 SPECT as a biomarker to scale up or step down treatment with immune-modulating drugs in a personalized fashion.