Hypericin as a marker for determination of tissue viability after radiofrequency ablation in a murine liver tumor model.
ABSTRACT 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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ABSTRACT: Hypericin (HYP) has been found avid to necrosis in small animal studies. We sought to evaluate the tissue distribution of (131)I-HYP in a large animal model and to explore the theranostic utilities of (131)I-HYP after radiofrequency ablation (RFA).La radiologia medica 07/2014; · 1.46 Impact Factor
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ABSTRACT: Residual cancer cells and subsequent tumor relapse is an obstacle for curative cancer treatment. Tumor necrosis therapy (TNT) has recently been developed to cause residual tumor regression or destruction. Here, we exploited the avidity of the sennidin A (SA) tracer and radioiodinated SA (131I-SA) to necrotic tumors in order to further empower TNT. We showed high uptake and prolonged retention of SA in necrotic tumors and a quick clearance in other non-targeted tissues including the liver. On SPECT-CT images, tumor mass appeared persistently as a hotspot. Based on the prominent targetability of 131I-SA to the tumor necrosis, we designed a combinational theragnostic modality. The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) was used to cause massive tumor necrosis, which formed the target of 131I-SA that subsequently killed the residual tumor cells by cross-fire irradiation of beta particles. Consequently, 131I-SA combined with CA4P significantly inhibited tumor growth, extended tumor doubling time and prolonged mean animal survival. In conclusion, 131I-SA in combination with necrosis inducing drugs/therapies may generate synergetic tumoricidal effects on solid malignancies by means of primary debulking and secondary cleansing process.Oncotarget 05/2014; 5(10):2934-46. · 6.64 Impact Factor
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ABSTRACT: The aim of this study was to investigate the necrosis avid agent hypericin as a potential indicator for determination of myocardial infarction (MI). Male Sprague-Dawley rats (n=30) weighing 350±20 g were subjected to acute reperfused MI. Animals were divided into 4 groups (n=6), in which hypericin was intravenously injected at 0, 1, 2, and 5 mg/kg, respectively. One day after injection, rats were euthanized with their hearts excised for qualitative and quantitative studies by means of microscopic fluorescence examination to decide the dosage of hypericin. Another group was injected with hypericin at the decided dose and evaluated by fluorescence macroscopy in colocalization with triphenyltetrazoliumchloride (TTC) and histomorphology. Infarct-to-normal contrast ratio and relative infarct size were quantified. Hypericin-induced red fluorescence was significantly brighter in necrotic than in viable myocardium as proven by a 6-times higher mean fluorescence density. Mean MI area was 35.66 ± 22.88% by hypericin fluorescence and 32.73 ± 21.98% by TTC staining (R(2) =0.9803). Global MI-volume was 34.56 ± 21.07% by hypericin and 35.11±20.47% by TTC staining (R(2) = 0.9933). The results confirm that hypericin specifically labeled necrosis, and enhanced the imaging contrast between the infarcted and normal myocardium, suggesting its potential applications for the assessment of myocardial viability. This article is protected by copyright. All rights reserved.Photochemistry and Photobiology 01/2014; · 2.29 Impact Factor