The Importance of Intratumor Temperature Uniformity in the Study of Radiosensitizing Effects of Hyperthermia in Vivo

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Abstract
An improved technique for water bath heating of murine tumors s.c. implanted on the flank is described. A rapid intratumor temperature rise to within 0.1.degree. C of bath temperature is achieved by loosely constricting the skin beneath the tumor with a special clip. The conventional heating method without the clip is characterized by a protracted intratumor temperature rise and tumor temperatures at depth which remain more than 0.5.degree. C below bath temperature even after 1 h of heating. Tumors implanted in the gastrocnemius muscle and on the dorsum of the hind foot were similarly evaluated. The temperature curves associated with the leg tumors were only slightly better than those of the flank tumors and, similarly, foot tumors were slightly inferior to flank tumors heated with the clip. 133Xe clearance studies demonstrated no significant effect of the clip on tumor blood flow. X-ray dose-response studies of C3H mouse mammary tumors following heating for 1 h at 43.degree. C demonstrated a significantly reduced TCD[tissue culture dose]50/20 as a result of the clip. Thermal enhancement ratios were 1.9 for heating with the clip vs. 1.5 for that without the clip. The temperature gradients and protracted thermal equilibration typical of leg and conventionally heated flank tumors apparently can result in tumor thermal enhancement ratios which are substantially too low. Previous reports based on these techniques must be considered accordingly.

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