Comparative study of iodine-123-labeled hypericin and 99mTc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction.

TitleComparative study of iodine-123-labeled hypericin and 99mTc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction.
Publication TypeJournal Article
Year of Publication2013
AuthorsCona MM, Feng Y, Li Y, Chen F, Vunckx K, Zhou L, Van Slambrouck K, Rezaei A, Gheysens O, Nuyts J, Verbruggen A, Oyen R, Ni Y
JournalJournal of cardiovascular pharmacology
Volume62
Issue3
Pagination304-11
Date Published2013 Sep
Abstract

Identification of myocardial infarction (MI) by imaging is critical for clinical management of ischemic heart disease. Iodine-123-labeled hypericin (I-Hyp) is a new potent infarct avid agent. We sought to compare target selectivity and organ distribution between I-Hyp and the myocardial perfusion agent, technetium-99m-labeled hexakis [2-methoxy isobutyl isonitrile] (Tc-Sestamibi) in rabbits with acute MI. Hypericin was radiolabeled with I using iodogen as oxidant, and Tc-Sestamibi was prepared from a commercial kit and radioactive sodium pertechnetate. Rabbits (n = 6) with 24-hour-old MI received I-Hyp intravenously and received Tc-Sestamibi 9 hours later. They were studied by dual-isotope simultaneous acquisition micro single photon emission computed tomography/computed tomography (DISA-μSPECT/CT), tissue gamma counting (TGC), autoradiography, and histology. After purification, I-Hyp was obtained with radiochemical purity around 99%. DISA-μSPECT/CT images showed I-Hyp retention in infarcted but not in normal myocardium. By TGC, accumulation values reached 1.175 ± 0.096 percentage of injected dose per gram (%ID/g) and 0.028 ± 0.007%ID/g in infarcted myocardium and normal myocardium with high tracer concentration in liver, intestines, and gallbladder. Tc-Sestamibi was prepared with radiochemical purity over 95%. DISA-μSPECT/CT showed no accumulation in MI and high initial radioactivity levels in normal myocardium that were rapidly cleared as confirmed by TGC (0.011 ± 0.003%ID/g). Liver and intestines were clearly visualized. By TGC, gallbladder and kidneys show moderate Tc-Sestamibi uptake. The selectivity of I-Hyp for infarcted myocardium and Tc-Sestamibi for normal myocardium was confirmed. I-Hyp distribution in rabbits is characterized by hepatobiliary excretion. Tc-Sestamibi undergoes hepatorenal elimination.

DOI10.1038/ng.2653
Alternate JournalJ. Cardiovasc. Pharmacol.