NEOVASCULARIZATION INDUCED GROWTH OF IMPLANTED C6 GLIOMA MULTICELLULAR SPHEROIDS - MAGNETIC-RESONANCE MICROIMAGING

Magnetic resonance imaging has been used to follow noninvasively tumor neovascularization and tumor growth in a model system of multicellula r C6 rat glioma spheroids implanted s.c. in nude mice. By positioning a single spheroid approximately 1 cm from the site of incision both th e vascularization of the tumor and the wound healing processes were sp atially separated and could be simultaneously followed. The model prop osed here provides defined initial conditions of tumor geometry and ce ll proliferative status and separation of initial tumor growth from ne ovascularization. Magnetic susceptibility relaxation provided an intri nsic marker for blood containing vessels. The implanted spheroid induc ed vessel growth within 4 days after implantation that was geometrical ly oriented toward the spheroid and distinct from wound healing at the site of incision. Volume measurements showed a corresponding 4-day la g in growth followed by Gompertz progression. Sham implantation of aga rose beads of similar diameter shelved no induction of vessel growth, ruling out a direct effect of wound healing. The new vessels penetrati ng the tumor were highly permeable to the contrast reagent gadolinium- diethylenetriaminepentaacetic acid. This permeability may be due to th e action of vascular endothelial growth factor, a major angiogenic gro wth factor in this system, and a potent permeability factor.