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Increased Thermal Response to Ultrasound in the Walker Carcinosarcoma Treated with Vasoactive Drugs

Institute for Nuclear Medicine, German Cancer Research Center, D-6900 Heidelberg, Federal Republic of Germany

In order to evaluate the potential of a highly selective Ca²⁺ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2–0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 ± 1.9 (SD) to 1.74 ± 0.86 as determined by intraarterial ¹³³Xe injection; i.p. injection of 2–8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 ± 2.67 to 1.3 ± 1.59. During a 20-min period of 41°C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 ± 0.9°C (N = 16). Nisoldipine or 5-HT injection at continuing 41°C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 ± 1.14°C or 44.2 ± 1.26°C, respectively, after a period of 20 min. Injection of 0.9% (NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

¹ To whom requests for reprints should be addressed, at Institute of Nuclear Medicine, Heart Center of North-Rhine Westphalia, Georgstr. 11, D-4970 Bad Oeynhausen, FRG.

Received 1/ 7/88. Revised 9/ 1/88. Revised 1/ 4/89. Accepted 1/ 6/89.