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Leuven, Belgium

Mulier S.,Theragnostic Laboratory | Mulier S.,CHIREC Cancer Institute | Jiang Y.,Theragnostic Laboratory | Wang C.,Federal University of Pampa | And 4 more authors.
International Journal of Hyperthermia

Purpose: The aim of this study was to develop an electrode system with simple needle electrodes which would allow a reliable and predictable ablation zone with radiofrequency ablation (RFA). Materials and methods: In the first step, four parallel electrodes (active length 3cm, diameter 1.8mm) were inserted in ex vivo bovine liver. A power of 50W was applied between two pairs of electrodes for 10min or until current shut-off due to impedance rise. In the second step, the influence of changing inter-electrode distance on coagulation size and geometry was measured. In the third step, a finite element method (FEM) analysis of the experiment was performed to better understand the experimental findings. Results: A bipolar four-electrode system with templates adjusting the inter-electrode distance was successfully developed for ex vivo experiments. A complete and reliable coagulation zone of a 3×2×2-cm block was obtained most efficiently with an inter-electrode distance of 2cm in 5.12±0.71min. Above 2cm, coagulation was incomplete due to a too low electric field, as demonstrated by the FEM analysis. Conclusions: The optimal inter-electrode distance of the present bipolar four-electrode system was 2cm, allowing a reliable and predictable ablation zone in ex vivo liver. The FEM analysis correctly simulated and explained the findings in ex vivo liver. The experimental set-up may serve as a platform to gain more insight and to optimise the application of RFA by means of four or more simple needle electrodes. © 2012 Informa UK Ltd All rights reserved. Source

Wang C.,China Pharmaceutical University | Wang C.,Jiangsu Province Academy of Traditional Chinese Medicine | Jin Q.,Jiangsu Province Academy of Traditional Chinese Medicine | Yang S.,Jiangsu Province Academy of Traditional Chinese Medicine | And 10 more authors.
Molecular Pharmaceutics

An innovative anticancer approach targeted to necrotic tissues, which serves as a noncancerous and generic anchor, may present a breakthrough. Necrosis avid agents with a flat conjugate aromatic structure selectively accumulate in necrotic tissues, but they easily form aggregates that undesirably distribute to normal tissues. In this study, skyrin, a dianthraquinone compound with smaller and distorted -cores and thus decreased aggregates as compared with hypericin (Hyp), was designed to target necrosis for tumor therapy. Aggregation studies of skyrin by UV/vis spectroscopy showed a smaller self-association constant with skyrin than with Hyp. Skyrin was labeled by iodine-131 with a radiochemical purity of 98% and exhibited good stability in rat serum for 72 h. In vitro cell uptake studies showed significant difference in the uptake of 131I-skyrin by necrotic cells compared to normal cells (P < 0.05). Compared in rats with liver and muscle necrosis, radiobiodistribution, whole-body autoradiography, and SPECT/CT studies revealed higher accumulation of 131I-skyrin in necrotic liver and muscle (p < 0.05), but lower uptake in normal organs, relative to that of 131I-Hyp. In mice bearing H22 tumor xenografts treated with combretastatin A4 disodium phosphate, the highest uptake of 131I-skyrin was found in necrotic tumor. In conclusion, 131I-skyrin appears a promising agent with reduced accumulation in nontarget organs for targeted radionuclide therapy of solid tumors. © 2015 American Chemical Society. Source

Gao M.,Jiangsu Province Academy of Traditional Chinese Medicine | Yao N.,Jiangsu Province Academy of Traditional Chinese Medicine | Huang D.,Jiangsu Province Academy of Traditional Chinese Medicine | Jiang C.,Jiangsu Province Academy of Traditional Chinese Medicine | And 9 more authors.
Journal of Drug Targeting

The aim of the present study is to verify the trapping effect of combretastatin A-4-phosphate (CA4P) on small molecular drugs in rodent tumors. Mice with H22 hepatocarcinoma were randomized into groups A and B. Magnetic resonance imaging (MRI) of T1WI, T2WI, and DWI was performed as baseline. Mice in group A were injected with Gd-DTPA and PBS. Mice in group B were injected with Gd-DTPA and CA4P. All mice undergo CE-T1WI at 0 h, 3 h, 6 h, 12 h, and 24 h. Enhancing efficacy of the two groups on CE-T1WI was compared with the signal-to-noise ratio (SNR) calculated. Concentrations of gadolinium measured by ICP-AES in the tumor were compared between groups. On the early CE-T1WI, tumors were equally enhanced in both groups. On the delayed CE-T1WI, the enhancing effect of group A was weaker than that of group B. The SNR and the concentration of gadolinium within the tumor of group A were lower than that of group B at 6 h, 12 h, and 24 h after administration. This study indicates that CA4P could improve the retention of Gd-DTPA in the tumor and MRI allowed dynamically monitoring trapping effects of CA4P on local retention of Gd-DTPA as a small molecular drug. © 2015 Informa UK Ltd. Source

Liu X.,Jiangsu Province Academy of Traditional Chinese Medicine | Liu X.,Nanjing University | Feng Y.,Jiangsu Province Academy of Traditional Chinese Medicine | Feng Y.,Theragnostic Laboratory | And 17 more authors.
Journal of Drug Targeting

Hypericin is a necrosis avid agent useful for nuclear imaging and tumor therapy. Protohypericin, with a similar structure to hypericin except poorer planarity, is the precursor of hypericin. In this study, we aimed to investigate the impact of this structural difference on self-assembly, and evaluate the necrosis affinity and metabolism in the rat model of reperfused hepatic infarction. Protohypericin appeared less aggregative in solution compared with hypericin by fluorescence analysis. Biodistribution data of 131I-protohypericin showed the percentage of injected dose per gram of tissues (%ID/g) increased with time and reached to the maximum of 7.03 at 24h in necrotic liver by gamma counting. The maximum ratio of target/non-target tissues was 11.7-fold in necrotic liver at 72h. Pharmacokinetic parameters revealed that the half-life of 131I-protohypericin was 14.9h, enabling a long blood circulation and constant retention in necrotic regions. SPECT-CT, autoradiography, and histological staining showed high uptake of 131I-protohypericin in necrotic tissues. These results suggest that 131I-protohypericin is a promising necrosis avid compound with a weaker aggregation tendency compared with hypericin and it may have a broad application in imaging and oncotherapy. © 2015 Informa UK Ltd. Source

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