Hypericin as a marker for determination of tissue viability after radiofrequency ablation in a murine liver tumor model

Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, B-3000 Leuven, Belgium.
Oncology Reports (Impact Factor: 2.3). 04/2008; 19(4):927-32. DOI: 10.3892/or.19.4.927
Source: PubMed


In this proof-of-principle study, the necrosis avid agent hypericin was investigated as a potential indicator for early therapeutic response following radiofrequency ablation (RFA) of murine liver tumors. Eight mice bearing intrahepatic RIF-1 tumors were intravenously injected with hypericin 1 h before or 24 h after RFA treatment. Mice were euthanized 24 h after hypericin injection and excised livers were investigated by means of fluoromacroscopic and fluoromicroscopic examinations in combination with conventional histomorphology. Significant differences in hypericin fluorescence were found in necrosis, viable tumor and normal liver tissue in a decreasing order: in necrosis, mean fluorescence densities were about 5 times higher than in viable tumor and approximately 12 times higher than in normal liver (p<0.05). Mean fluorescence densities were not significantly different when hypericin was injected 24 h after or 1 h before RFA treatment (p>0.05). As a conclusion, hypericin features the property to specifically enhance the imaging contrast between necrotic and viable tissues and to non-specifically distinguish viable tumor from normal liver. The results suggest that hypericin offers significant potential in the early assessment of response following necrosis-inducing antineoplastic treatments such as RFA.

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    • "In a murine model, Van de Putter et al. 11 studied hypericin as a potential imaging biomarker for early monitoring of therapeutic response after radiofrequency ablation (RFA) of liver tumors. Taking advantage of the compound's fluorescent property, they used a fluoromicroscope to show that the mean hypericin fluorescence density in necrosis was about 5 times and 12 times higher than in viable tumor and normal liver tissue, respectively. "
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    ABSTRACT: Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [(123)I]iodohypericin, [(124)I]iodohypericin, and [(131)I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin.
    Full-text · Article · Aug 2013 · Theranostics
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    • "During a recent contrast agent study, Ni et al further expanded the role of Hyp in medicine by revealing that the necrosis avidity of Hyp is superior to its tumor affinity6,11,12,13. Therefore, the necrosis avidity of radioiodinated Hyp, such as [123I]iodohypericin (123I-Hyp), has been used as a diagnostic tool for imaging ischemic myocardial infarction and therapeutic tumor necrosis11,12,13,14,15,16,17. Additionally, the potential use of 131I-Hyp for the treatment of cancer has been investigated with encouraging results, which have been demonstrated in rodent tumor models13,15. "
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    ABSTRACT: Aim: Hypericin (Hyp) and its radio-derivatives have been investigated in animal models with ischemic heart diseases and malignancies for diagnostic and therapeutic purposes. Before radioiodinated Hyp (123I-Hyp or 131I-Hyp) can be considered as a clinically useful drug, vigorous evaluations on its chemotoxicity are necessary. In the present study, we examined the toxicity of a single dose of non-radioactive 127I-Hyp in normal mice for 24 h and 14 d. Methods: Studies were performed on 132 normal mice. 127I -Hyp at a clinically relevant dose of 0.1 mg/kg body weight and a 100-times higher dose of 10 mg/kg was intravenously injected into 40 mice. The safety aspects of clinical manifestations, serological biochemistry, and histopathology were assessed. In another 72 mice, 127I-Hyp was administered intravenously at assumed values to bracket the value of LD50. The rest 20 mice were used in the control groups. Results: At 24 h and 14 d following the injection of 127I -Hyp at either 0.1 or 10 mg/kg, all mice tolerated well without mortality or any observable treatment-related symptoms. No significant differences were found in blood biochemical parameters between the test and control groups. All organs presented normal appearances upon histopathological inspection. The value of LD50 of 127I-Hyp in mice through intravenous injection was 20.26 mg/kg, with the 95% confidence interval between 18.90 and 21.55 mg/kg. Conclusion: The current study reveals a broad safety range of 127I-Hyp, which not only supports the use of 123I-Hyp or 131I-Hyp in the necrosis targeting theragnostic strategy, but also serves as a valuable reference for exploring other possible applications for iodinated Hyp.
    Full-text · Article · Oct 2012 · Acta Pharmacologica Sinica
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    ABSTRACT: Following the footprint of porphyrin-mediated photodynamic therapy (PDT), paramagnetic metalloporphyrins were originated as tumor seeking contrast agents (CAs) for magnetic resonance imaging (MRI). However, serial research has disproved their tumor selectivity, identified nonviable tissues as their real targets, and eventually elicited new applica-tions in myocardial infarction delineation, tissue viability evaluation, ablation therapy assessment, as well as first pass or dynamic perfusion MRI, multi-organ contrast enhancement (CE), atherosclerotic plaque imaging and stem cell labeling or tracking. Furthermore, nonporphyrin analogues have been developed to reduce porphyrin related toxicities. These porphy-rin and nonporphyrin compounds have been termed as necrosis-avid contrast agents (NACAs) to denote their major dis-covered affinity. The present review aims to document the evolving research in this particular field, to discuss possible mechanisms, to promote further preclinical and clinical development of this unique and promising class of MRI CAs, and to implicate a novel stroma targeting strategy for diagnosis and treatment of malignant and benign disorders.
    Full-text · Article · May 2008 · Current Medical Imaging Reviews
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