Sensitizer for photodynamic therapy of cancer: A comparison of the tissue distribution of photofrin ii and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor

Abstract

The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.

Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for topically applied photosensitizers

“…ence of uptake time for Photofrin. This may be due to the fact that Photofrin is taken up more slowly [52] than the other sensitizers used in this study. In fact, for the relatively short uptake times (up to 90 min) in the present study, the uptake kinetics was rate limiting.…”

“…One distinguishes between 'fast'-and 'slow'-acting photosensitizers, having characteristic elimination half-lives (t 1/2 ) in plasma. For example, for lipophilic Photofrin t 1/2 s8 h [52], for PpIX t 1/2 s2 h [41], for hydrophilic AlPcS n t 1/2 s1.5 h [52], whereas for liposomally encapsulated BPD t 1/2 s20 min [4]. However, with topical application on the CAM, less difference is expected than with systemic administration, since uptake through the extremely thin ectoderm is dominated by diffusion, which is of the same order of magnitude for molecules having similar molecular weights.…”

Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration

“…administration, although absolute drug concentrations were higher in some organs (liver and kidney) after i.v. administration (Bellnier et al, 1989;Peng et al, 1991). Photofrin levels in the bladder were not measured in these studies.…”

“…Detectable levels of the fluorescent component of Photofrin were, however, present in the normal bladder for up to 10 days. Drug uptake and distribution studies in mice have also demonstrated a slow clearance of these sensitisers from other normal tissues (Peng et al, 1991;Bellnier et al, 1989), with detectable drug levels in muscle, skin, heart, lung, spleen, kidney and liver at 75 days after injection of 5 mg kg-' Photofrin (Bellnier et al, 1989). Several studies have also demonstrated longer elimination times for Photofrin (plasma and tissue) after i.p.…”

In vivofluorescence imaging for tissue diagnostics

“…Phthalocyanines are interesting, as many of them have a much stronger fluorescence than HpD, and at longer wavelengths with less overlap with the tissue autofluorescence (Spikes 1986). A better selectivity for malignant tissues has also been found (van Leengoed et al 1990, Peng et al 1991. Other PDT drugs examined for fluorescence tumour marking capabilities include chlorins (mono-aspartyl chlorin e 6 (MACE), di-aspartyl chlorin e 6 (DACE), meso-tetra hydroxyphenyl chlorin (mTHPC) and benzoporphyrin derivatives (Roberts et al 1988, Andersson-Engels et al 1993, Alian et al 1994.…”