A comparative study of tissue distribution and photodynamic therapy selectivity of chlorin e6, Photofrin II and ALA-induced protoporphyrin IX in a colon carcinoma model.

G Kostenich,Z Malik,L Roitman,Y Kopolovic,Y Shechtman,B Ehrenberg,A Orenstein

doi:10.1038/bjc.1996.185

Abstract

An in vivo study of tissue distribution kinetics and photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA), chlorin e6 (Chl) and Photofrin (PII) was performed to evaluate the selectivity of porphyrin accumulation and tissue damage effects in a tumour model compared with normal tissue. C26 colon carcinoma of mice transplanted to the foot was used as a model for selectivity assessment. Fluorescence measurements of porphyrin accumulation in the foot bearing the tumour and in the normal foot were performed by the laser-induced fluorescence (LIF) system. A new high-intensity pulsed light delivery system (HIPLS) was used for simultaneous irradiation of both feet by light in the range of 600-800 nm, with light doses from 120 to 300 J cm-2 (0.6 J cm-2 per pulse, 1 Hz). Photoirradiation was carried out 1 h after injection of ALA, 3 h after injection of Chl and 24 h after injection of PII. A ratio of porphyrin accumulation in tumour vs normal tissue was used as an index of accumulation selectivity for each agent. PDT selectivity was determined from the regression analysis of normal and tumour tissue responses to PDT as a function of the applied light dose. A normal tissue damage index was defined at various values (50, 80 and 100%) of antitumour effect. The results of the LIF measurements revealed different patterns of fluorescence intensity in tumour and normal tissues for ALA-induced protoporphyrin IX (ALA-PpIX), Chl and PII. The results of PDT demonstrated the differences in both anti-tumour efficiency and normal tissue damage for the agents used. The selectivity of porphyrin accumulation in the tumour at the time of photoirradiation, as obtained by the LIF measurements, was in the order ALA-PpIX > Chl > PII. PDT selectivity at an equal value of anti-tumour effect was in the order Chl > ALA-PpIX > PII. Histological examination revealed certain differences in structural changes of normal skin after PDT with the agents tested. The results of PDT selectivity assessment with respect to differences in mechanisms of action for ALA, Chl and PII are discussed.

Highlights

Results of the photodynamic therapy (PDT) study using photoirradiation by high-intensity pulsed light delivery system (HIPLS) revealed that both the anti-tumour effect and the normal tissue damage index were enhanced with increasing light doses for all agents (Figures 6 and 8)
The results of the present study showed that with the treatment regimens used chlorin e6 (Chl) was more effective than Photofrin II (PII) and aminolaevulinic acid (ALA)-induced PpIX for inhibition of tumour growth (Figure 6), and caused minimal damage to normal tissue (Table I)
The results demonstrated that oedema of the normal foot after ALA-PDT with light doses of 120-180 J cm-2 was more pronounced than after Chl-PDT or PH-PDT, but when the light doses increased, normal tissue damage was less than for PII-PDT (Figure 8, Table I)