Tc-99m-CXCL8 SPECT to monitor disease activity in inflammatory bowel disease

Rationale: Inflammatory bowel diseases (IBD) 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. A total of 30 patients (15 Crohns' disease, 15 Ulcerative colitis) participated and 92 segmental pairs of histology and Tc-99m-CXCL8 scan were studied. Imaging was performed after injection of 400 MBq Tc-99m-CXCL8. Planar and SPECT acquisitions of the abdomen were performed 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 was 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, was 82% and 72%, negative predictive value was 81% and the overall positive predictive value was 74%. Using different cut-offs, specificity could be increased at the expense of sensitivity. In 74 segmental pairs, overall sensitivity and specificity for endoscopy was 74% and 85%, and PPV of 81% and NPV of 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.

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