Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models

OBJECTIVES The present animal experiments were conducted to evaluate radioiodinated Hypericin (Hyp) for its regional distribution as well as theranostic potentials. MATERIALS AND METHODS Rat models of reperfused liver infarction (RLI) and hepatic rhabdomyosarcoma (R1) were surgically induced. R1 models received Combretastatin A4 phosphate (CA4P) intravenously at 10 mg/kg 24 h prior to radioiodinated Hyp. Three groups of 6 rats each containing 3 RLI and 3 R1 models received iv injections of (123)I-Hyp at 37, 74, and 185 MBq/kg respectively and followed by 0.1 ml of 1% Evans blue solution were sacrificed at 4, 24 and 48 hour post injection immediately after in vivo examination of MRI and planar gamma scintigraphy. Besides, two groups of 6 R1 models that received either 300 MBq/kg of (131)I-Hyp or vehicle intravenously were examined using MRI to compare tumor growth for 12 days. Autoradiography, gamma counting, and histopathology were performed for postmortem verifications and quantification. RESULTS Necrosis as seen in vivo on contrast-enhanced MRI corresponded well with the hot spots on planar scintigraphy. Autoradiography and gamma counting revealed intense accumulation of (123)I-Hyp in necrotic liver (3.94 ± 1.60, 5.38 ± 1.04, and 6.03 ± 2.09 %ID/g ± SD) and necrotic tumor (4.27 ± 0.76, 5.57 ± 0.76, and 5.68 ± 1.33 %ID/g ± SD) relative to normal liver (1.76 ± 0.54, 0.41 ± 0.18, and 0.16 ± 0.07 %ID/g ± SD), with a high necrosis-to-liver ratio of 2.3, 14.0, and 37.0 at 4, 24 and 48 h respectively. Tumor volumes in R1 models that received (131)I-Hyp and vehicle changed from 0.45 ± 0.09, and 0.47 ± 0.12 cm(3) (p > 0.05) on day 0 to1.32 ± 0.76 and 3.63 ± 0.72 cm(3 )(p < 0.001) on day 12, with the corresponding necrosis ratios from 73 ± 12 %, and 76 ± 17 % to 47 ± 18% and 17 ± 13 % (p < 0.01), and with the tumor DT of 7.3 ± 1.0 and 4.2 ± 0.7 days, respectively. CONCLUSIONS Radioiodinated Hyp as a necrosis avid tracer appears promising for non-invasive imaging diagnosis of necrosis-related pathologies. Its prominent targetability to necrosis allows targeted radiotherapy for malignancies on top of a prior necrosis-inducing treatment.