Rousseau J, Boyle R W, Maclennan A H, Truscott T G, Van Lier J E
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Int J Rad Appl Instrum B. 1991;18(7):777-82. doi: 10.1016/0883-2897(91)90017-f.
To evaluate the biodistribution and tumor uptake of chlorogallium tetraoctadecycloxy phthalocyanine, a potential new drug for the photodynamic therapy of cancer, we prepared the radioactive 67Ga-labeled complex and its water soluble sulfonated derivative. The non-sulfonated dye was obtained by condensation of octadecyloxyphthalonitrile in the presence of a mixture of 67Ga and 69Ga chloride. The sulfonated derivative was obtained by treatment of the condensation product with oleum. As singlet molecular oxygen has been implicated in the photodynamic action of phthalocyanines (Pcs), the quantum yield of singlet oxygen (phi delta) was evaluated for chlorogallium tetraoctadecyloxy Pc, and also its zinc, aluminum and metal free analogues. After intraperitoneal administration of the non-sulfonated dye into RIF tumor bearing C3H mice, a very high 67Ga-uptake was observed in the spleen, while tumor radioactivity remained low during the 3 day study. The in vivo stability of the 67Ga-phthalocyanine complex was confirmed by comparing the distribution pattern with that of 67Ga-citrate, which proved to be significantly different. Intravenous injection of the sulfonated dye resulted in an overall lowering of 67Ga-uptake by most tissues, particularly in the spleen, while tumor radioactivities were slightly higher. These data suggest that amphiphilic photosensitizers, containing both polar sulfonate groups and long aliphatic substituents, exhibit the best distribution pattern for both imaging and photodynamic therapy of tumors.
为评估四十八烷氧基酞菁氯镓（一种潜在的癌症光动力治疗新药）的生物分布和肿瘤摄取情况，我们制备了放射性67Ga标记的复合物及其水溶性磺化衍生物。通过在67Ga和69Ga氯化物混合物存在下使十八烷氧基邻苯二腈缩合得到非磺化染料。磺化衍生物通过用发烟硫酸处理缩合产物获得。由于单线态分子氧与酞菁（Pcs）的光动力作用有关，因此评估了四十八烷氧基酞菁氯镓及其锌、铝和无金属类似物的单线态氧量子产率（φδ）。将非磺化染料腹腔注射到荷RIF肿瘤的C3H小鼠体内后，在脾脏中观察到非常高的67Ga摄取，而在为期3天的研究中肿瘤放射性仍然很低。通过将分布模式与67Ga-柠檬酸盐的分布模式进行比较，证实了67Ga-酞菁复合物的体内稳定性，结果证明两者有显著差异。静脉注射磺化染料导致大多数组织中67Ga摄取总体降低，尤其是在脾脏中，而肿瘤放射性略高。这些数据表明，同时含有极性磺酸根基团和长脂肪族取代基的两亲性光敏剂在肿瘤成像和光动力治疗方面均表现出最佳的分布模式。
