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 exten t and severity of inflammatory bowel disease. Currently, the radiopharmaceu tical of choice is Tc-99m-hexamethyl propyleneamine oxime (HMPAO)-leukocyte s. We studied the imaging potential of two recently developed Tc-99m-labele d agents, polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinat e (HYNIC) IgG, in a rabbit model of acute colitis, and compared them with t hat of Tc-99m-labeled, granulocyte-enriched (>90%), white blood cells. Meth ods: Acute colitis was induced in rabbits by retrograde instillation of tri nitrobenzene 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 kill ed, and the uptake of the radiolabel in the dissected tissues was determine d. For each affected 5-cm segment, the colitis index (Cl, affected-to-norma l-colon-uptake ratio) was calculated and correlated to the macroscopically scored severity of inflammation. Results: All three agents visualized the c olitis lesions within 1 hr postinjection. The Cl correlated with the severi ty of the abnormalities. With increasing severity, the Cl at 4 hr postinjec tion 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 1 0.61 +/- 1.34, respectively. The Cl for the other two agents did not change significantly with time. Conclusion: In this rabbit model, Tc-99m-labeled granulocytes, IgG and liposomes 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 im age inflammatory bower disease, because they can be prepared off the shelf and no handling of blood is required.