Effects of hyperthermia on bioenergetic status and phosphorus T1S in humanmelanoma xenografts monitored by P-31-MRS

Conventional hyperthermia enhances tumor response to radiotherapy through t hermal cell inactivation and vascular shut-down, whereas mild hyperthermia potentiates the effect of radiotherapy by improving tumor oxygenation. The work reported here was aimed at investigating whether P-31-magnetic resonan ce spectroscopy (P-31-MRS) measurements of tumor bioenergetic status; i,e,, the (PCr + NTP beta)/P-i resonance ratio, and/or the spin lattice relaxati on times, T(1)s, of the P-i and NTP beta resonances can be used to distingu ish between the effects of conventional and mild hyperthermia. BEX-t human melanoma xenografts were treated at 43.0 degrees C for 15 or 60 min, and bi oenergetic status and T(1)s were measured as function-of-time after treatme nt. Hyperthermia-induced effects on tumor blood how was measured by using t he Rb-86 uptake method. The morphology of the capillary network in treated and untreated tumors was studied by histologic examination. Tumors treated for 15 min showed increased blood flow and dilated capillaries, whereas tum ors treated for 60 min showed decreased blood flow and capillary occlusions ; i.e., 43.0 degrees C for 15 min was a treatment consistent with mild hype rthermia and 43.0 degrees C for 60 min was consistent with conventional hyp erthermia treatment of BEX-t tumors. Bioenergetic status increased after tr eatment at 43.0 degrees C for 15 min, and decreased after treatment at 43.0 degrees C for 60 min, similar to the blood how, Likewise, the T-1 of the P -i resonance increased after treatment at 43.0 degrees C for 15 min, and de creased after treatment at 43.0 degrees C for 60 min. The T-1 of the NTP be ta resonance showed a similar change as the T-1 of the P-i resonance, but l ess pronounced. Consequently, P-31-MRS measurements of tumor bioenergetic s tatus and the T-1 of the P-i resonance may perhaps be utilized to distingui sh between vascular effects of mild and conventional hyperthermia. (C) 1999 Elsevier Science Inc.