Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours.
The possibility of enhancing aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) by simultaneous application of localised hyperthermia (HT) was evaluated. Treatments of rat DS-sarcomas included: (i) control, (ii) ALA administration (375 mg kg(-1), i.p.), no illumination, (iii) 'nonthermal' illumination, (iv) ALA-PDT: that is, ALA administration, 'nonthermal' illumination, (v) localised HT, 43 degrees C, 60 min (vi) ALA-PDT+HT: ALA administration with full spectrum irradiation resulting in ALA-PDT and HT. Tumour volume was monitored for 90 days or until a target volume (3.5 ml) was reached. No differences were seen between the first three groups, with all tumours reaching the target volume by 8-11 days. A total of 13 and 15% of tumours did not reach the target volume by day 90 following HT or ALA-PDT treatment, respectively. ALA-PDT+HT showed the greatest antitumour effect (P=0.0001), with 61% of the tumours not reaching the target volume. Viability and in vitro growth were also assessed in cells from tumours excised after treatment. ALA-PDT+HT reduced the fraction of viable tumour cells by 85%, and in vitro culture showed pronounced growth delay compared to control cells. These results demonstrate an enhanced antitumour effect upon ALA+HT, which appears to involve direct cell toxicity rather than solely vascular damage.
Kelleher
D K
DK
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany. kelleher@uni-mainz.de
Bastian
J
J
Thews
O
O
Vaupel
P
P
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012509:Sarcoma / Q000188:drug therapy* / Q000662:veterinary; D016896:Treatment Outcome
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid