Aprahamian M, Evrard S, Keller P, Tsuji M, Balboni G, Damgé C, Marescaux J
INSERM, Unit 61, Digestive Cell Biology and Physiopathology, Strasbourg, France.
Anticancer Drug Des. 1993 Apr;8(2):101-14.
The in vivo administration and distribution of a potent new photosensitizer, pheophorbide A (PH-A), was investigated in rats. The spectral characteristics were determined. This hydrophobic compound was solubilized by an ethanol/phosphate-buffered saline (PBS) mixture (v/v) and sonicated immediately before i.v. administration. Tissue distribution and the affinity of PH-A for an acinar pancreatic tumor were determined in Lewis rats for up to 48 h after a single i.v. administration of 3 mg kg-1 body wt. Methanol-extracted PH-A was quantitatively determined by fluorescence spectrophotometry at 665.6 nm. The PH-A uptake pattern showed that the reticulo-endothelial system is the major target of PH-A, followed by the gut and then the lung and pancreas. PH-A concentrations in skin were very low. The presence of an enterohepatic cycle was suggested by the PH-A biliary output, intestinal uptake and blood concentrations. Tumor PH-A retention was longer than pancreatic retention. The ratio of tumoral to peri-tumoral pancreas PH-A was 6.7:1, 24 h after i.v. administration. With its similar tissue pattern, better absorption spectrum and lower skin toxicity, PH-A could be a more potent photosensitizer than hematoporphyrin derivatives.
在大鼠体内研究了一种强效新型光敏剂脱镁叶绿酸A（PH-A）的给药及分布情况。测定了其光谱特征。这种疏水性化合物用乙醇/磷酸盐缓冲盐水（PBS）混合物（体积比）溶解，并在静脉注射前立即进行超声处理。在Lewis大鼠单次静脉注射3mg/kg体重后长达48小时内，测定了PH-A在组织中的分布及其对胰腺腺泡肿瘤的亲和力。通过荧光分光光度法在665.6nm处对甲醇提取的PH-A进行定量测定。PH-A的摄取模式表明，网状内皮系统是PH-A的主要靶点，其次是肠道，然后是肺和胰腺。皮肤中的PH-A浓度非常低。PH-A的胆汁排出、肠道摄取和血液浓度提示存在肝肠循环。肿瘤中PH-A的保留时间比胰腺中的长。静脉注射后24小时，肿瘤与肿瘤周围胰腺的PH-A比值为6.7:1。由于其相似的组织模式、更好的吸收光谱和更低的皮肤毒性，PH-A可能是一种比血卟啉衍生物更有效的光敏剂。
