Magnetic resonance imaging identifies early effects of sunitinib treatment in human melanoma xenografts.
BACKGROUND
Antiangiogenic treatment may change the tumor microenvironment and hence influence the effect of conventional therapies. The potential of diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced MRI (DCE-MRI) in assessing microenvironmental effects of sunitinib treatment was investigated in this preclinical study.


METHODS
Sunitinib-treated and untreated A-07 tumors were subjected to DW-MRI and DCE-MRI, and parametric images of ADC and Ktrans were produced. Microvascular density, hypoxic fraction, and necrotic fraction were assessed from immunohistochemical preparations, and tumor interstitial fluid pressure (IFP) was assessed with probe measurement.


RESULTS
Sunitinib-treated tumors showed reduced microvascular density, increased hypoxic fraction, increased necrotic fraction, increased ADC, and reduced Ktrans, but did not differ from untreated tumors in growth rate and IFP.


CONCLUSIONS
Sunitinib treatment affected the tumor microenvironment without affecting tumor size. DW-MRI and DCE-MRI were sensitive to the sunitinib-induced changes in the tumor microenvironment.
Department of Radiation Biology, Group of Radiation Biology and Tumor Physiology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo N-0310, Norway. Jon.Vidar.Gaustad@rr-research.no.
Jon-Vidar
JV
Gaustad
Viktoria
V
Pozdniakova
Tord
T
Hompland
Trude G
TG
Simonsen
Einar K
EK
Rofstad
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D018328:Melanoma, Amelanotic / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011758:Pyrroles / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D000077210:Sunitinib; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib