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in Sorret band (380 nm) with the help of LED or 532 nm laser in Q-band. Instruments allowed to registrate luminescence at 645 and 615 nm with temporal resolution from 5 to 2000 microseconds. Biodistribution was investigated ex vivo time-dependent manner from 0.5 to 21 h Pt-CP accumulation in living mice. Results: LD100 for Pt-TPP(p-COOH)4 and Pt-CP was 12.5 and 200mg/kg of an animal’s weight, LD50 was 8 and 120mg/kg, and maximum tolerance dose (MTD) was 6.25 and 80mg/kg, respectively. Pt-TPP(p-COOH)4 causes sharp dose-dependent leucocytosis during the first week after injection. Autopsy indicate dose-dependent infarct-like change of myocardial structure. No other organ pathology was detected. It was found that body weight losses depended on injection dose, while number of leucocytes did not depend on dose. Animals’ death in this case was caused by heart damage. Thus, Pt-TPP(p-COOH)4 possesses acute toxicity: body mass loss, leucocytosis, cardiopathology and early death. For Pt-CP, less pronounced leucocytosis and cardiotoxicity are accompanied with noticeable intestinal reaction. Pt-CP intravenous injection in dose 0.02mg/kg resulted in its accumulation in all organs, accumulation maximum being after 1 2 h post injection. Tumor revealing contrast (ratio of luminescence intensity between tumor and normal muscle tissue) was equal to 3 5 times (to normal tissues). That ratio was practically independent from accumulation time, but it was in direct dependence from vascularization degree of tumor tissue (up to 20 30 times in some areas). Pt-CP limit of detection in the tumor was ~0.002mg/kg of an animal’s weight. Tumor revealing contrast gave comparable results on excitation with LED or laser. Conclusions: In summary, it was demonstrated that water-soluble Pt-CP displayed fairly good characteristics in animal tissues and can be potentially used as nonphototoxic diagnostic reagents for luminescent tumor detection in concentrations significantly lower than MTD. The work was supported with project 3065 ISTC. |
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