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 99mTc-hexamethyl propyleneamine oxime (HMPAO)-leukocytes. We studied the imaging potential of two recently developed 99mTc-labeled agents, polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinate (HYNIC) IgG, in a rabbit model of acute colitis, and compared them with that of 99mTc-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 (CI, 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 CI correlated with the severity of the abnormalities. With increasing severity, the CI 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 CI further increased during 24-hr postinjection to 6.56+/-0.84, 8.50+/-0.53 and 10.61+/-1.34, respectively. The CI for the other two agents did not change significantly with time.


CONCLUSIONS
In this rabbit model, 99mTc-labeled granulocytes, IgG and liposomes all rapidly visualized colonic inflammation. Granulocytes and liposomes showed the highest CI. 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.
Dams
E T
ET
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Oyen
W J
WJ
Boerman
O C
OC
Storm
G
G
Laverman
P
P
Koenders
E B
EB
van der Meer
J W
JW
Corstens
F H
FH
D000818:Animals; D001345:Autoradiography; D003092:Colitis / Q000000981:diagnostic imaging*; D004337:Drug Carriers; D005260:Female; D006098:Granulocytes; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D008081:Liposomes; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D019690:Technetium Tc 99m Exametazime / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C099153:technetium Tc 99m hydrazinonicotinate-IgG; D019690:Technetium Tc 99m Exametazime; D011092:Polyethylene Glycols