Intratumor heterogeneity in perfusion in human melanoma xenografts measured by contrast-enhanced magnetic resonance imaging.
The perfusion in tumors shows substantial spatial heterogeneity compared to that in normal tissues. The aim of the present study was to evaluate the intratumor heterogeneity in perfusion in tumors of two amelanotic human melanoma xenograft lines, A-07 and R-18, grown intradermally in Balb/c nu/nu mice. A non-invasive contrast-enhanced magnetic resonance imaging method yielding results in absolute values was applied. The perfusion was determined in manually defined regions of interest, corresponding to a whole tumor or to subregions of a tumor. The mean perfusion and the intertumor heterogeneity 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 in 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 substantially larger than the intertumor heterogeneity in A-07 tumors, whereas in R-18 tumors, the intratumor heterogeneity was similar to the intertumor heterogeneity. These observations imply that measurements of mean tumor perfusion may have limited value as a predictive assay for outcome of treatment.
Bjørnaes
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I
Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. ingvil.bjornas@dnr.uio.no
Lyng
H
H
Dahle
G A
GA
Kaalhus
O
O
Rofstad
E K
EK
D000230:Adenocarcinoma / Q000098:blood supply; D000818:Animals; D006224:Cricetinae; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply; D018328:Melanoma, Amelanotic / Q000098:blood supply* / Q000628:therapy; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D008962:Models, Theoretical; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply; D011379:Prognosis; D051381:Rats; D012513:Sarcoma, Experimental / Q000098:blood supply; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured