Technetium-99m-labeled liposomes to image experimental colitis in rabbits: Comparison with technetium-99m-HMPAO-granulocytes and technetium-99m-HYNIC-IgG

Scintigraphic techniques are routinely used for the evaluation of the extent and severity of inflammatory bowel disease. Currently, the radiopharmaceutical of choice is 99m Tc-hexamethyl propyleneamine oxime (HMPAO)-leukocytes. We studied the imaging potential of two recently developed 99m Tc-labeled agents, polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinate (HYNIC) IgG, in a rabbit model of acute colitis, and compared them with that of 99m Tc-labeled, granulocyte-enriched (>90%), white blood cells. Methods: Acute colitis was induced in rabbits by retrograde instillation of trinitrobenzene sulfonic acid. After 48 hr, 37 MBq of each radiopharmaceutical was administered intravenously. Gamma camera images were taken at 0, 1, 2, 4, 10 and 24 hr. At 4 and 24 hr postinjection, groups of rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. For each affected 5-cm segment, the colitis index (Cl, affected-to-normal-colon-uptake ratio) was calculated and correlated to the macroscopically scored severity of inflammation. Results: All three agents visualized the colitis lesions within 1 hr postinjection. The Cl correlated with the severity of the abnormalities. With increasing severity, the Cl at 4 hr postinjection for liposomes was 3.89 ± 0.73, 4.41 ± 0.47 and 5.76 ± 0.65; for IgG 1.67 ± 0.08, 3.92 ± 0.44 and 6.14 ± 0.65; and for granulocytes 2.90 ± 0.09, 6.15 ± 0.96 and 9.36 ± 3.35. For liposomes, the Cl further increased during 24-hr postinjection to 6.56 ± 0.84, 8.50 ± 0.53 and 10.61 ± 1.34, respectively, The Cl for the other two agents did not change significantly with time. Conclusion: In this rabbit model, 99m Tc-labeled granulocytes, IgG and liposomes f all rapidly visualized colonic inflammation. Granulocytes and liposomes showed the highest Cl. Technetium-99m-labeled PEG-liposomes may be an attractive alternative for labeled leukocytes to image inflammatory bowel disease, because they can be prepared off the shelf and no handling of blood is required.