RT Journal Article SR Electronic T1 Rapid Imaging of Experimental Colitis with 99mTc-Interleukin-8 in Rabbits JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 917 OP 923 VO 42 IS 6 A1 Stefan Gratz A1 Huub J.J.M. Rennen A1 Otto C. Boerman A1 Wim J.G. Oyen A1 Frans H.M. Corstens YR 2001 UL http://jnm.snmjournals.org/content/42/6/917.abstract AB 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.