title: Clinical pharmacokinetic studies of tetra(meta-hydroxyphenyl)chlorin in squamous cell carcinoma by fluorescence spectroscopy at 2 wavelengths.
abstract: To optimize photodynamic therapy (PDT) and photodetection of cancer with second-generation photosensitizers, knowledge of important variables such as the uptake of the dye and the dye contrast between normal and tumoral tissue after injection is necessary. The pharmacokinetics of a second-generation photosensitizer, tetra(meta-hydroxyphenyl)chlorin (mTHPC), is presented. To study this in a clinical context, an apparatus based on fluorescence spectroscopy and a noninvasive optical fiber probe has been used. The mTHPC fluorescence is induced at 2 excitation wavelengths (420 and 520 nm) with different penetration depth. The pharmacokinetics of mTHPC in patients with a squamous-cell carcinoma in the oral cavity show a signal selectivity as high as 16 about 3 hr after 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 obtained at 420 and 520 nm show little difference. These pharmacokinetics can be used directly for optimizing photodetection with mTHPC. However, complementary information on the localization of the drug by fluorescence microscopy, and a correlation of this data with tumor necrosis efficacy, are needed to optimize PDT timing.
authors.affiliation: Institut de Génie de l'Environnement, Ecole Polytechnique Fédérale, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Braichotte
authors.forename: J F
authors.initials: JF
authors.lastname: Savary
authors.forename: T
authors.initials: T
authors.lastname: Glanzmann
authors.forename: P
authors.initials: P
authors.lastname: Westermann
authors.forename: S
authors.initials: S
authors.lastname: Folli
authors.forename: G
authors.initials: G
authors.lastname: Wagnieres
authors.forename: P
authors.initials: P
authors.lastname: Monnier
authors.forename: H
authors.initials: H
authors.lastname: Van den Bergh
mesh_terms: D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008652:Mesoporphyrins / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence
chemical_list: D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; C072269:temoporfin