Rapid imaging of experimental colitis with Tc-99m-interleukin-8 in rabbits

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 radio labeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with Tc-99m using hyd razinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of Tc-99m-HMPAO-labeled granulocyte s, Methods: In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically Visualized after injection of either 1L-8 or purified granulocytes, both labeled with (TC)-T-99m, Gamma camera images w ere acquired at 2 min and at 1, 2, and 4 h after injection. Four hours afte r injection, the rabbits were killed, and the uptake of the radiolabel in t he 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. Tc-99m-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously in creased until 4 h after injection, whereas no further increase 1 h after in jection was noticed scintigraphically for Tc-99m-HMPAO-granulocytes. The ab solute uptake in the affected colon was much higher for IL-8 than for the r adiolabeled 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, respectiv ely, With increasing severity, the CI at 4 h after injection for 99mTc-HYNI C-IL-8 was 4.4 +/- 0.6, 13.5 +/- 0.5, and 25.8 +/- 1.0; for granulocytes, t he 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). Conclus ion: Within 1 h after injection, visualization of the extent of colonic inf lammation in vivo was possible with Tc-99m-HYNIC-IL-8 and Tc-99m-HMPAO-gran ulocytes. Within 2 h after injection, Tc-99m-IL-8 allowed a good evaluation , and within 4 h after injection, a meticulous evaluation of the severity o f IBD. Although Tc-99m-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of i nflammation was not possible. Tc-99m-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. 99mTc-IL-8 can be prepar ed off-the-shelf and yields excellent imaging with high target-to-backgroun d ratios.