Evaluation of Necrosis Avidity and Potential for Rapid Imaging of Necrotic Myocardium of Radioiodinated Hypocrellins.

Rapid noninvasive delineation of necrotic myocardium in ischemic regions is very critical for risk stratification and clinical decision-making but still challenging. This study aimed to evaluate the necrosis avidity of radioiodinated hypocrellins and its potential for rapidly imaging necrotic myocardium.

The aggregation constants of four natural hypocrellins were analyzed by UV/vis spectroscopy. Then, they were radiolabeled with iodine-131 by iodogen oxidation method. Necrosis avidity of iodine-131-labeled hypocrellins was evaluated in rat models with reperfused liver infarction and muscular necrosis by gamma counting, autoradiography, and histopathology. Their pharmacokinetic properties were examined in normal rats. The potential of iodine-131-labeled hypomycin A ([131I]HD) for early imaging of necrotic myocardium was explored in rat models with reperfused myocardial infarction. Finally, the possible mechanism of necrosis avidity was investigated by in vitro DNA binding and in vivo blocking experiments.

The aggregation constants of four hypocrellins were all much smaller than that of hypericin, a most studied necrosis avid agent. The radiochemical purities of the four radiotracers after purification were all greater than 95 %, and more than 90 % of tracers remained intact after incubation in rat serum for 24 h. Among the four tracers, [131I]HD exhibited the highest necrotic to viable tissue uptake ratio and the fastest blood clearance. The necrotic myocardium could be clearly visualized 4 h after injection of [131I]HD by single-photon emission computed tomography/X-ray computed tomography (SPECT/CT). DNA binding studies suggested that HD could bind to DNA through intercalation. Blocking studies demonstrated that uptake of [131I]HD in necrotic muscle could be significantly blocked by excess unlabeled HD and ethidium bromide with 67 and 60 % decline at 6 h after coinjection, respectively.

[131I]HD can be used to rapidly visualize necrotic myocardium. The necrosis avidity mechanism of [131I]HD may be attributed to its binding to the exposed DNA in necrotic tissues.