BIODISTRIBUTION OF A METHYLENE-BLUE DERIVATIVE IN TUMOR AND NORMAL-TISSUES OF RATS

By using a chemical extraction procedure and confocal laser scanning f luorescence microscopy we have investigated the kinetic patterns of up take and biolocalization of a methylene blue derivative (MBD) in tumor s and various normal tissues of Wistar rats bearing fibrosarcoma (Leed s ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body w eight). Similar kinetics of accumulation and elimination of MBD fluore scence were found in tumor tissue and surrounding normal skin and musc le tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h af ter intravenous injection, indicating selective uptake of MBD by the t umor tissue. MBD was localized on the walls of all the vessels and ext ensively in the area of neoplastic cellular and tumorigenic fibrous co mponents in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph no des. In the skin, MBD was mainly distributed in the keratinized epithe lium of the epidermis, hair follicles and their accessories, while lit tle was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injec tion, after which it decreased dramatically to almost undetectable lev els 120 h postinjection. Strong fluorescence of MBD was seen in the tr acheal mucosal epithelium, while little fluorescence was noted in the transitional epithelium of bladder. The kinetics of biolocalization of MBD in some other tissues (liver, spleen, kidney, brain, muscle, lung , heart) were also studied.