CLINICAL PHARMACOKINETIC STUDIES OF TETRA(META-HYDROXYPHENYL)CHLORIN IN SQUAMOUS-CELL CARCINOMA BY FLUORESCENCE SPECTROSCOPY AT 2 WAVELENGTHS

To optimize photodynamic therapy (PDT) and photodetection of cancer wi th second-generation photosensitizers, knowledge of important variable s such as the uptake of the dye and the dye contrast between normal an d tumoral tissue after injection is necessary. The pharmacokinetics of a second-generation photosensitizer, tetra(meta-hydroxyphenyl) chlori n (mTHPC), is presented. To study this in a clinical context, an appar atus based on fluorescence spectroscopy and a noninvasive optical fibe r probe has been used. The mTHPC fluorescence is induced at 2 excitati on wavelengths (420 and 520 nm) with different penetration depth. The pharmacokinetics of mTHPC in patients with a squamous-cell carcinoma i n the oral cavity show a signal selectivity as high as 16 about 3 hr a fter i.v. injection for the more advanced carcinomas. The magnitude of this selectivity appears to correlate with the staging of the cancer, the more invasive tumors showing the highest selectivity. Results obt ained at 420 and 520 nm show little difference. These pharmacokinetics can be used directly for optimizing photodetection with mTHPC. Howeve r, complementary information on the localization of the drug by fluore scence microscopy, and a correlation of this data with tumor necrosis efficacy, are needed to optimize PDT timing. (C) 1995 Wiley-Liss, Inc.