Increased efficacy of photodynamic therapy of R3230AC mammary adenocarcinoma by intratumoral injection of Photofrin II

Abstract

Summary Photodynamic therapy consists of the systemic administration of a derivative of haematoporphyrin (Photofrin 11) followed 24-72 h later by exposure of malignant lesions to photoradiation. We investigated the efficacy of this treatment after direct intratumoral injection of Photofrin II. This direct treatment regimen resulted in higher rates of inhibition of mitochondrial cytochrome c oxidase (5.13% J' cmM2 x 10-') and succinate dehydrogenase (3.14% J-' cm-2 X 10-I) in vitro at 2 h after intratumoral injection compared to rates of inhibition obtained after intraperitoneal drug administration: 0.51 and 0.42% J -I cm-2 x 10-', respectively. A significant delay in tumour growth in vivo was observed in animals that received intratumoral injections 2 h before photoradiation compared to animals injected intraperitoneally at either 2 or 24 h before photoradiation. The treatment protocols were compared with control groups, consisting of Photofrin II administration intratumorally or intraperitoneally without photoradiation, or photoradiation in the absence of Photofrin II. These data indicate that the intratumoral injection regimen with Photofrin II enhanced the efficacy of photodynamic therapy. The greater delay in tumour growth observed after intratumoral administration of Photofrin II suggests a mechanism favouring direct cell damage.

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy

“…At 24 h after PDT irradiation, the level E P-NTP/Pi ratios remained significantly reduced compared to all pre-treatment control levels. Inter- (Figure 6), followed by a gradual return to near pretreatment levels by [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] h, a finding which is in agreement with other investigators (Naruse et al, 1986b;Chopp et al, 1987Chopp et al, , 1990 (Ceckler et al, 1986;Hilf et al, 1987 (Gibson et al, 1990).…”

Photodynamic therapy of cancer — Challenges of multidrug resistance

“…[77][78][79] The e®ectiveness and safety of intratumoral injection of PS can be a®ected by drug formulation, injection volume, velocity and site. The use of lipid-based PS (e.g., Foscan) and nanocarriers might improve the PS distribution and retention in targeted tumor.…”

Response of Photofrin®-sensitised mesothelioma xenografts to photodynamic therapy with 514 nm light

“…The purpose of the present study was to extend this earlier work and to identify criteria for a somewhat more quantitative dosimetry at this treatment wavelength. Our goal was to establish treatment conditions at 514 nm that produced long-term delays in the regrowth of human mesothelioma xenografts that were similar to those that had been previously reported using 630 nm irradiation (Gibson et al, 1994 (Gibson et al, 1990a). Results of the 514 nm PDT treatment protocols were compared with data obtained using 630 nm irradiation (50 mW cm-2, 2 h), a subset of which was previously published (Gibson et al, 1994).…”