Segalla A, Fedeli F, Reddi E, Jori G, Cross A
Department of Biology, University of Padova, Italy.
Int J Cancer. 1997 Jul 17;72(2):329-36. doi: 10.1002/(sici)1097-0215(19970717)72:2<329::aid-ijc21>3.0.co;2-9.
The efficiency and selectivity of tumour targeting by several tetra-n-propylporphycene (TPPn) and tetrakis(methoxyethyl)porphycene (TMPn) derivatives have been studied by administering 3.76 micromol/kg of aqueous or liposomal porphycene formulations to BALB/c mice bearing an i.m. implanted MS-2 fibrosarcoma. These 2 parameters have been studied as a function of the type of substituents linked to the 9-position of the macrocycle by amide, ester or ether functional groups. The pharmacokinetic properties appear to be controlled mainly by the degree of porphycene hydrophobicity, as evaluated by measuring their retention times in a C 18 column for HPLC. Thus, the post-injection time (T50) at which the porphycene concentration in the plasma decreases to 50% of the initial value ranged from a few minutes for the less hydrophobic to several hours for the more hydrophobic porphycenes. An increase in hydrophobicity also was accompanied by an enhanced efficiency and selectivity of tumour targeting. The less hydrophobic porphycenes showed a maximum tumour uptake of 0.5-2 nmol/g of tissue at 10-20 min after administration with a tumour/peri-tumoural concentration ratio around 2-3, while those with higher hydrophobicity reached tumour concentrations of 7-8 nmol/g at 24-48 hr after administration with concentration ratios higher than 20.
通过给接种了肌肉注射植入的MS-2纤维肉瘤的BALB/c小鼠注射3.76微摩尔/千克的水溶或脂质体卟啉制剂，研究了几种四正丙基卟啉（TPPn）及四（甲氧基乙基）卟啉（TMPn）衍生物对肿瘤靶向的效率和选择性。这两个参数作为酰胺、酯或醚官能团连接到大环9位上的取代基类型的函数进行了研究。通过测量它们在用于高效液相色谱的C18柱中的保留时间来评估，药代动力学性质似乎主要由卟啉的疏水性程度控制。因此，血浆中卟啉浓度降至初始值50%时的注射后时间（T50），对于疏水性较低的卟啉为几分钟，对于疏水性较高的卟啉为几小时。疏水性增加还伴随着肿瘤靶向效率和选择性的提高。疏水性较低的卟啉在给药后10 - 20分钟时显示出最大肿瘤摄取量为0.5 - 2纳摩尔/克组织，肿瘤/肿瘤周围浓度比约为2 - 3，而疏水性较高的卟啉在给药后24 - 48小时达到肿瘤浓度为7 - 8纳摩尔/克，浓度比高于20。
