Theranostics 2012; 2(10):1010-1019. doi:10.7150/thno.4924

Research Paper

Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models

Junjie Li1,2, Marlein Miranda Cona1,2, Feng Chen1,2, Yuanbo Feng1,2, Lin Zhou3, Jie Yu1, Johan Nuyts3, Peter de Witte4, Jian Zhang5, Uwe Himmelreich2, Alfons Verbruggen4, Yicheng Ni1,2,5✉

1. Theragnostic Laboratory, Department of Imaging & Pathology, Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
2. Molecular Small Animal Imaging Centre/MoSAIC, Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
3. Nuclear Medicine & Medical Imaging, Department of Imaging & Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
4. Faculty of Pharmaceutical Sciences, Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
5. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, China

Abstract

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 123I-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 131I-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 123I-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 131I-Hyp and vehicle changed from 0.45 ± 0.09, and 0.47 ± 0.12 cm3 (p > 0.05) on day 0 to1.32 ± 0.76 and 3.63 ± 0.72 cm3 (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.

Keywords: Radioiodinated Hypericin, Theranostic, Necrosis avidity, Malignancies.

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How to cite this article:
Li J, Cona MM, Chen F, Feng Y, Zhou L, Yu J, Nuyts J, de Witte P, Zhang J, Himmelreich U, Verbruggen A, Ni Y. Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models. Theranostics 2012; 2(10):1010-1019. doi:10.7150/thno.4924. Available from http://www.thno.org/v02p1010.htm