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: Stanislaw Schastak, Benedikt Jean, Romy Handzel, Genady Kostenich, Ralf Hermann, Ulrich Sack, Arie Orenstein, Yu-Sheng Wang, Peter Wiedemann
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 78 Issue 3 Pg. 203-13 (Mar 01 2005) ISSN: 1011-1344 [Print] Switzerland
• PMID: 15708517 (Publication Type: Journal Article)

Chemical References

• Photosensitizing Agents
• Porphyrins

Topics

• Animals
• Cell Line, Tumor
• Humans
• Infrared Rays
• Magnetic Resonance Spectroscopy
• Mice
• Mice, Inbred BALB C
• Necrosis
• Photosensitizing Agents (adverse effects, pharmacokinetics)
• Porphyrins (adverse effects, pharmacokinetics)
• Spectrophotometry, Ultraviolet
• Tissue Distribution