Intratumor heterogeneity in perfusion in human melanoma xenografts measured by contrast-enhanced magnetic resonance imaging

The perfusion in rumors shows substantial spatial heterogeneity compared to that in normal tissues. The aim of the present study was to evaluate the i ntratumor heterogeneity in perfusion in rumors of two amelanotic human mela noma xenograft lines, A-07 and R-18, grown intradermally in Balb/c nu/nu mi ce. A non-invasive contrast-enhanced magnetic resonance imaging method yiel ding results in absolute values was applied. The perfusion was determined i n manually defined regions of interest, corresponding to a whole tumor or t o subregions of a tumor. The mean perfusion and the intertumor heterogeneit y in perfusion were similar for the two tumor lines. For whole A-07 tumors, the perfusion ranged from 0.089 mL/(g . min) to 0.20 mL/(g . min) [mean: 0 .15 mL/(g . min)], and for whole R-18 tumors, from 0.030 mL/(g . min) to 0. 17 mL/(g . min) [mean: 0.13 mL/(g . min)]. The intratumor heterogeneity, on the other hand, was estimated to be 6.4 times larger in A-07 tumors than i n R-18 tumors. The highest perfusion values, up to 0.69 mL/(g . min), were found in subregions of A-07 tumors. The intratumor heterogeneity was substa ntially larger than the intertumor heterogeneity in A-07 tumors, whereas in R-18 tumors, the intratumor heterogeneity was similar to the intertumor he terogeneity. These observations imply that measurements of mean tumor perfu sion may have limited value as a predictive assay for outcome of treatment. (C) 2000 Elsevier Science Inc. All rights reserved.