Bellnier D A, Henderson B W, Pandey R K, Potter W R, Dougherty T J
Division of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY 14263.
J Photochem Photobiol B. 1993 Sep;20(1):55-61. doi: 10.1016/1011-1344(93)80131-r.
The combination of the new photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) and laser light of wavelength 665 nm showed antitumor activity against two s.c.-implanted murine tumors. HPPH also sensitized normal mouse foot tissue to light but photosensitivity decreased rapidly with time after HPPH administration. Mechanistic studies revealed that HPPH induced little direct tumor cell toxicity but was an effective mediator of vascular photodamage. Pharmacokinetic studies following intravenous injection of 1 mg [14C]HPPH per kilogram revealed a biexponential decay with time, with plasma alpha and beta half-lives of 0.69 and 21 h respectively. Fecal excretion was the primary route of elimination. The highest levels of [14C]HPPH were found in the liver, which also showed the greatest long-term retention. The sequence of decreasing uptake levels was the liver, adrenals, lung, spleen, kidney, urinary bladder, heart, eye, skin, pancreas, muscle, testes, fat and brain. This distribution correlated with the relative blood perfusion rates in the tissues.
新型光动力敏化剂2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a（HPPH）与波长665nm的激光联合使用，对两种皮下植入的小鼠肿瘤显示出抗肿瘤活性。HPPH也使正常小鼠足部组织对光敏感，但在给予HPPH后，光敏性随时间迅速降低。机制研究表明，HPPH几乎不诱导直接的肿瘤细胞毒性，而是血管光损伤的有效介质。静脉注射每千克1mg[14C]HPPH后的药代动力学研究显示，其随时间呈双指数衰减，血浆α和β半衰期分别为0.69小时和21小时。粪便排泄是主要的消除途径。在肝脏中发现[14C]HPPH的水平最高，肝脏也显示出最大的长期滞留。摄取水平降低的顺序为肝脏、肾上腺、肺、脾、肾、膀胱、心脏、眼睛、皮肤、胰腺、肌肉、睾丸、脂肪和脑。这种分布与组织中的相对血液灌注率相关。
