title: Improved pharmacokinetics, biodistribution and necrosis in vivo using a new near infra-red photosensitizer: tetrahydroporphyrin tetratosylat.
abstract: The search for better photosensitizers for photodynamic therapy of malignancies has led to the investigation of a new water-soluble, positively charged, and chemical stable tetrahydroporphyrin tetratosylat (THPTS) with a strong absorption at 760.5 nm, belonging to the bacteriochlorophyll family. THPTS undergoes a rapid uptake by human choroidal melanoma (CM) cells with a weak dark toxicity after a 24-h incubation (LD10 = 150 microM, LD50 = 6.0 mM). In response to laser light at 760+/-3 nm and doses of 10, 15 and 30 J/cm2, around 71%, 76%, and 92% of the CM cells were killed, respectively. Studies of pharmacokinetics and biodistribution in vivo (living mice) and ex vivo (excised organs) were made in a Balb/c mice bearing subcutaneously inoculated C26 colon carcinoma using fiber-optic spectrofluorimetry (FOS). Tumours were irradiated 3 h after intraperitoneal (i.p.) injection of 5.0 mg/kg THPTS with an incoherent light source at 750+/-20 nm and an intensity of 100 mW/cm2 and fluences of 60, 90 and 120 J/cm2. THPTS demonstrated preferential accumulation in C26 colon carcinoma in comparison with most normal tissues except kidneys. For the tissues of liver, colon, muscle, and spleen the tumour/normal tissue ratio (TNTR) ranged from 8.0 to 50. After irradiation with 120 J/cm2 the depth of tumour necrosis reached 15 mm. Histological examination of the tumour samples 24 h after THPTS-PDT, revealed severe stasis in the blood vessels and coagulative necrosis. These results suggest that THPTS-PDT may be of particular importance in the treatment of accessible malignancies.
authors.affiliation: Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Augenheilkunde, Liebig Strasse 10-14, 04103 Leipzig, Germany. stas@medizin.uni-leipzig.de
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Schastak
authors.forename: Benedikt
authors.initials: B
authors.lastname: Jean
authors.forename: Romy
authors.initials: R
authors.lastname: Handzel
authors.forename: Genady
authors.initials: G
authors.lastname: Kostenich
authors.forename: Ralf
authors.initials: R
authors.lastname: Hermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.forename: Arie
authors.initials: A
authors.lastname: Orenstein
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007259:Infrared Rays; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000009:adverse effects / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins