Ferumoxtran-10 enhancement in orthotopic xenograft models of human brain tumors: an indirect marker of tumor proliferation?
OBJECTIVE
Ferumoxtran-10 belongs to the Ultra Small Particles of Iron Oxide (USPIO) class of contrast agents and induces delayed tumor enhancement in brain tumors, reflecting the trapping of iron oxide particles by the macrophages and activated microglia. The aim of the study was to compare Ferumoxtran-10 contrast enhancement in four human high-grade glioma xenograft models (TCG2, TCG3, TCG4, and U87) with different growing profiles.


METHODS
Fragments of human malignant glioma were orthotopically xenografted into the brain of four groups of nude mice. All mice underwent a MRI examination 24 h after intravenous administration of Ferumoxtran-10 (axial T1 SE weighted MR images). The contrast enhancement observed in the different tumor types was measured and was correlated to in vivo tumor growth and to histological parameters, such as proliferative tumor cell fraction, apoptosis, vascular density, and Perls' staining score.


RESULTS
A good relationship was observed: (a) between tumor-to-background contrast and proliferative index, (b) between tumor-to-background contrast and tumor growth, and (c) between tumor-to-background contrast and Perls' staining score. The registered MR enhancement contrasts were not influenced by apoptotic index and by vascular density in these experimental xenografts.


CONCLUSIONS
Tumor contrast enhancement 24 h after intravenous Ferumoxtran-10 administration seems to be well correlated to tumor proliferative index and tumor growth and could be used as an indirect marker of tumor proliferation.
Kremer
Stéphane
S
Service de Neuro-Radiologie, Hôpital Central, CHRU Nancy, Nancy, France. kremers@club-internet.fr
Pinel
Sophie
S
Védrine
Pierre-Olivier
PO
Bressenot
Aude
A
Robert
Philippe
P
Bracard
Serge
S
Plénat
François
F
D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects*; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D008819:Mice, Nude; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010087:Oxides / Q000493:pharmacokinetics*; D011859:Radiography; D014018:Tissue Distribution; D014183:Transplantation, Heterologous / Q000473:pathology
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide