Applegate Catherine C, Deng Hongping, Kleszynski Brittany L, Cross Tzu-Wen L, Konopka Christian J, Dobrucki L Wawrzyniec, Nelson Erik R, Wallig Matthew A, Smith Andrew M, Swanson Kelly S
Division of Nutritional Sciences, University of Illinois at Urbana - Champaign, Urbana, Illinois, USA.
Department of Animal Sciences, University of Illinois at Urbana - Champaign, Urbana, Illinois, USA.
J Exp Nanosci. 2022;17(1):599-616. doi: 10.1080/17458080.2022.2134563. Epub 2022 Oct 19.
The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe (Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.
炎症性肠病（IBD）在全球范围内的发病率正在上升。尽管目前用于IBD的诊断和疾病监测测试能够灵敏地检测肠道炎症，但它们缺乏正电子发射断层扫描（PET）的分子和细胞特异性。在这项概念验证研究中，我们使用通过口服、灌肠和腹腔内途径给药的放射性标记巨噬细胞靶向纳米载体探针（Cu-NOTA-D500），以评估在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中，生物分布对给药途径的依赖性，该模型涉及健康组织和患病组织。通过将肠道组织中探针摄取量标准化为肝脏或全肠道摄取量，可降低个体间肠道组织探针摄取的高变异性。对于口服和腹腔内途径，健康动物和DSS结肠炎动物肠道之间标准化摄取量的差异最大。肝脏绝对摄取量的差异反映了IBD病理学可能的二级诊断指标。这些结果应为针对IBD和相关肠道疾病的炎症靶向造影剂的临床前开发提供参考，以提高诊断准确性。
