Van de Putte Marie, Wang Huaijun, Chen Feng, de Witte Peter A M, Ni Yicheng
Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, University Hospital, K.U. Leuven, Herestraat 49, B-3000, Leuven, Belgium.
Acad Radiol. 2008 Jan;15(1):107-13. doi: 10.1016/j.acra.2007.08.008.
In this preclinical proof-of-principle study, the necrosis avid agent hypericin was investigated as a potential early indicator for therapeutic response after ethanol-mediated chemical ablation in murine liver tumors.
Seven mice bearing intrahepatic radiation-induced fibrosarcoma-1 tumors were intravenously injected with hypericin 1 hour before (n = 3) or 24 hours after (n = 4) intratumoral ethanol injection. Mice were euthanized 24 hours after hypericin injection and, taking advantage of the fluorescent property of the compound, the excised livers were investigated qualitatively and quantitatively by means of fluoromacroscopic and fluoromicroscopic examinations, colocalized with conventional histomorphology.
Significant differences in hypericin fluorescence were found in necrosis, viable tumor and normal liver tissue in decreasing order (P < .05) (ie, in necrosis, mean fluorescence densities were about 4.5 times higher than in viable tumor and approximately 14 times higher than in normal liver). When hypericin was injected 1 hour before, maximal blood concentrations were achieved at the time of ethanol treatment, so that on ablation an outstanding extravasation took place in the entire necrotic area in comparison with accumulation of hypericin only at the peripheral zone of necrosis when it was injected 24 hours after ablation.
Hypericin specifically enhanced the imaging contrast between necrotic and viable tissues and nonspecifically distinguished viable tumor from normal liver. Injection of hypericin shortly before ablation is more favorable than after ablation, because it circumvents difficulties with no-entry zones for hypericin and requires shorter intervals between ethanol ablation and imaging.
在这项临床前原理验证研究中，对坏死亲和剂金丝桃素作为小鼠肝肿瘤乙醇介导化学消融后治疗反应潜在早期指标进行了研究。
7只患有肝内辐射诱导纤维肉瘤-1肿瘤的小鼠，在瘤内注射乙醇前1小时（n = 3）或注射后24小时（n = 4）静脉注射金丝桃素。在注射金丝桃素24小时后对小鼠实施安乐死，并利用该化合物的荧光特性，通过荧光宏观和荧光显微镜检查对切除的肝脏进行定性和定量研究，并与传统组织形态学进行共定位。
在坏死组织、存活肿瘤组织和正常肝组织中，金丝桃素荧光存在显著差异，顺序递减（P <.05）（即，在坏死组织中，平均荧光密度比存活肿瘤组织高约4.5倍，比正常肝组织高约14倍）。当在乙醇治疗时，在注射金丝桃素1小时前注射，可达到最大血药浓度，因此与在消融后24小时注射时金丝桃素仅在坏死周边区域蓄积相比，消融时整个坏死区域出现明显的外渗。
金丝桃素特异性增强了坏死组织与存活组织之间的成像对比度，非特异性地区分了存活肿瘤与正常肝脏。在消融前不久注射金丝桃素比消融后注射更有利，因为它避免了金丝桃素无进入区的困难，并且乙醇消融与成像之间所需的间隔更短。
