Time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin and benzoporphyrin derivative monoacid ring A in the hamster model: Comparative fluorescence microscopy study

The pharmacokinetics of the photosensitizer used play a key role in the und erstanding of the mechanism of photodynamic therapy-induced damage. Fluores cence microscopy was used to compare time-dependent biodistribution of tetr a(m-hydroxyphenyl)chlorin (mTHPC) and benzoporphyrin derivative monoacid ri ng A (BPD-MA) in different hamster tissues, including an early, chemically induced, squamous cell carcinoma. Following injection of 0.5 mg/kg body wei ght of mTHPC and 2.0 mg/kg BPD-MA, groups of three animals were sacrificed at different time points and a series of fluorescence micrographs from diff erent excised organs were analyzed. The highest fluorescence intensities of mTHPC were observed at 96 h for squamous epithelia and skin and at 48 h fo r smooth muscle. There is no real peak of BPD-MA fluorescence between 30 mi n and 3 h in the basal epithelial layers, fibroconnective tissue, muscles o r blood vessels. At 4 h after injection, the fluorescence level of BPD-MA d ecreased and at 24 h it had returned to background level in all observed ti ssues. The significantly faster clearance of BPD-MA is the principal advant age as compared to mTHPC, However, similar localization patterns in differe nt tissues with essentially vascular affinity represent a possible disadvan tage for treating early malignancies with BPD-MA as compared to mTHPC, whic h is mainly localized in various epithelia, For both photosensitizers no si gnificant selectivity between early squamous cell carcinoma and healthy muc osae is seen. Pharmacokinetic studies of different photosensitizers in an a ppropriate animal model are essential for selecting new-generation photosen sitizers with the most favorable localization for photodynamic therapy of e arly malignancies in hollow organs.