Distribution and pharmacokinetics of Photofrin® in human bile duct cancer

https://doi.org/10.1016/S1011-1344(98)00203-6Get rights and content

Abstract

Prognosis of patients with bile duct tumors is mostly poor due to late diagnosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alternative treatment approach, we have investigated the uptake and tumor-specific localization of the photosensitizer Photofrin® in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin® in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosections. Fluorescence intensities (expressed as a percentage of a standard) are 19.0± 11.4% and 25.2 ± 12.7% for tumors and 10.9 ± 2.9% and 13.2 ± 9.1 % (mean ± SD) for normal bile duct tissue at 24 h (n = 5) and 48 h (n = 8) after Photofrin® administration (2 mg kg −1 i.V.), respectively, and decrease afterwards in normal bile duct tissue over the period of investigation (4–35 days). The ratios of fluorescence in tumor versus normal tissue are found to be 1.7 ± O.7 and 2.3 ± 1.2 (mean ± SD) at days one and two after Photofrin® administration, respectively. Thus, Photofrin® preferentially accumulates in bile duct neoplasms, reaching peak values during the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin® injection to achieve tumor selectivity of PDT for effective treatment of bile duct carcinoma.

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