Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment.
The effects of combined and simultaneously applied localised 43 degrees C hyperthermia (HT) and an antivascular bacteriochlorophyll-serine-based photodynamic therapy (Bchl-ser-PDT) on tumour growth and several microenvironmental parameters were examined. Rats bearing DS-sarcomas were allocated to treatment groups: (i) sham-treatment (control), (ii) Bchl-ser-PDT (20 mg kg(-1) i.v.), (iii) localised HT, (iv) Bchl-ser-PDT+HT. The light source used was an infrared-A irradiator, which, by use of appropriate filters, delivered the different ranges of wavelengths required. Following treatment, tumour volume was monitored. The greatest tumour growth inhibition was seen with Bchl-ser-PDT+HT, and subsequent experiments identified the pathophysiological basis for this effect. Red blood cell flux in tumour microvessels declined rapidly upon Bchl-ser-PDT+HT, reaching approximately 10% of initial values by the end of treatment. Similarly, tumour oxygenation worsened, reaching almost anoxic levels by the end of the treatment period. Assessment of metabolic parameters showed a pronounced increase in lactate levels and a decrease in ATP concentrations after combined treatment. The results presented suggest that vascular collapse and flow stasis resulting in a deterioration of tumour oxygenation and a switch from oxidative to glycolytic glucose turnover are key elements in the tumour eradication seen with this novel approach in which an antivascular PDT and HT are combined and simultaneously applied.
Kelleher
D K
DK
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University Mainz, Duesbergweg 6 D-55099 Mainz, Germany. kelleher@uni-mainz.de
Thews
O
O
Scherz
A
A
Salomon
Y
Y
Vaupel
P
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001429:Bacteriochlorophylls / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D003131:Combined Modality Therapy; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents