MR imaging in an experimental model of brain tumor immunotherapy.
A murine model of implanted CNS neoplasia was used to study a new form of brain tumor immunotherapy with intralesional Corynebacterium parvum (C. parvum). Assessment of treatment protocols has been limited by the inability to assess, noninvasively, tumor burden and/or the inflammatory reaction induced in the murine brain by treatment with C. parvum. This study demonstrates that contrast-enhanced MR imaging can monitor in vivo tumor burden and the immune response to intracerebral C. parvum. KHT murine sarcoma was stereotaxically implanted into the right frontal lobe of C3H/HeN mice at doses of 10,000 and 50,000 tumor cells. The KHT sarcoma is 100% fatal in untreated mice. Therapy consisted of an intraperitoneal injection of 350 micrograms of killed C. parvum 1 day after tumor implantation followed by 70 micrograms of C. parvum stereotaxically injected into the tumor 5 days after implantation. MR imaging was performed on mice injected with saline only, C parvum only, tumor only, and tumor treated with C. parvum. C. parvum alone elicited an intense transitory mononuclear cell inflammatory reaction in the meninges, ependyma, and to a variable degree at the injection site. The inflammatory response reached a peak 2 weeks after intracerebral injection. Contrast-enhanced MR imaging was able to detect the presence and severity of C. parvum-induced inflammation, which decreased 3 weeks after intracerebral injection. The transitory nature of this type of inflammation should allow its differentiation from tumor in subjects undergoing serial scanning following intracerebral injection of C. parvum as a form of brain tumor immunotherapy.
Blankenberg
F
F
Department of Radiology, #S072, Stanford University School of Medicine,CA 94305.
Conley
F K
FK
Sayre
J
J
Enzmann
D
D
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D009368:Neoplasm Transplantation; D011425:Propionibacterium acnes / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000628:therapy*