Distribution and pharmacokinetics of Photofrin (R) in human bile duct cancer

Prognosis of patients with bile duct tumors is mostly poor due to late diag nosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alte rnative treatment approach, we have investigated the uptake and tumor-speci fic localization of the photosensitizer Photofrin(R) in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin(R) in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosec tions. Fluorescence intensities (expressed as a percentage of a standard) a re 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(R) administration (2 mg kg(-1) i.v.), respectively , and decrease afterwards in normal bile duct tissue over the period of inv estigation (4-35 days). The ratios of fluorescence in tumor versus normal t issue are found to be 1.7 +/- 0.7 and 2.3 +/- 1.2 (mean +/- SD) at days one and two after Photofrin(R) administration, respectively. Thus, Photofrin(R ) preferentially accumulates in bile duct neoplasms, reaching peak values d uring the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin(R) injection to achieve tum or selectivity of PDT for effective treatment of bile duct carcinoma. (C) 1 998 Elsevier Science S.A. All rights reserved.