Comparison of the influence of a water-soluble polymer carrier on the tumor localization and biodistribution of mesotetrametahydroxyphenylchlorin (mTHPC) in two animal models

J.-P. Mach 1), Ph. Monnier 3) and H. van den Bergh 2)Institute of Biochemistry, University of LausanneInstitute of Environmental Engineering, LPAS, Swiss Federal Institute of Technology,CH-1O15 Lausanne, SwitzerlandENT Department, CHUV Hospital, LausanneABSTRACTMesotetrametahydroxyphenylchlorin (mTHPC) is compared to mTHPC derivatized withone or more polyethyleneglycol (PEG) chains of about 6000 amu. The latter compound iscalled mTHPC-PEG hereafter. In particular the uptake and removal of these two compoundsis studied in tumor and other tissues after injection as a function of the time. In afirst model this is done with nude mice bearing human colorectal xenografts (LS174T);in a second model it is studied in a chinese hamster with a 7,12 dimethylbenzanthracene(DMBA) induced early squamous cell carcinoma in the cheekpouch mucosa. In the nude micewith tumors grown to between 70 and 130 mg, tumor to muscle dye ratios are found toattain a maximum value of 4.8, eight hours after injection of mTHPC. With mTHPC-PEG thetumor to muscle ratio attained a value as high as 18.6, fourty-eight hours after injec-tion. In the hamster model the maximum tumor to normal mucosa ratio for mTHPC was about3.5 at times up to 2 hours after injection. For the mTHPC-PEG this ratio is always nearunity in this model.INTRODUCTIONAmong the multiple approaches taken to enrich dyes for hotodynamic therapy(PDT) and photodetection of early cancer in neoplastic tissue t) is the use of largewater-soluble dye carriers