Rapid Imaging of Experimental Colitis with 99mTc-Interleukin-8 in Rabbits

Journal of Nuclear Medicine

Frans H.M. Corstens¹  Wim J.G. Oyen¹  Huub J.J.M. Rennen¹  Stefan Gratz¹  Otto C. Boerman¹ 

[1] Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

关键词: inflammatory bowel disease;    interleukin-8;    granulocytes;    imaging infection;    technetium;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with 99mTc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of 99mTc-HMPAO-labeled granulocytes. Methods: In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with 99mTc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation. Results: Both agents visualized the colitis within 1 h after injection. 99mTc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for 99mTc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 ± 0.04 %ID/g and 0.09 ± 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for 99mTc-HYNIC-IL-8 was 4.4 ± 0.6, 13.5 ± 0.5, and 25.8 ± 1.0; for granulocytes, the CI at 4 h after injection was 1.5 ± 0.1, 3.4 ± 0.2, and 6.4 ± 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes). Conclusion: Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with 99mTc-HYNIC-IL-8 and 99mTc-HMPAO-granulocytes. Within 2 h after injection, 99mTc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although 99mTc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. 99mTc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. 99mTc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.

【 授权许可】

Unknown