Biodistribution of a methylene blue derivative in tumor and normal tissues of rats

By using a chemical extraction procedure and confocal laser scanning fluorescence microscopy we have investigated the kinetic patterns of uptake and biolocalization of a methylene blue derivative (MBD) in tumors and various normal tissues of Wistar rats bearing fibrosarcoma (Leeds ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body weight). Similar kinetics of accumulation and elimination of MBD fluorescence were found in tumor tissue and surrounding normal skin and muscle tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h after intravenous injection, indicating selective uptake of MBD by the tumor tissue. MBD was localized on the walls of all the vessels and extensively in the area of neoplastic cellular and tumorigenic fibrous components in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph nodes. In the skin, MBD was mainly distributed in the keratinized epithelium of the epidermis, hair follicles and their accessories, while little was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injection, after which it decreased dramatically to almost undetectable levels 120 h postinjection. Strong fluorescence of MBD was seen in the tracheal 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.