BRM Immunotherapy of Orthotopically Implanted Murine Bladder Tumours: Treatment Response by Monitoring MRI

The authors evaluated magnetic resonance imaging (MRI) for monitoring orthotopic bladder tumourgrowth and treatment response to intravesical immunotherapy with the biological response modifiers(BRMs): recombinant tumour necrosis factor alpha (TNF-α), combination of TNF-α plus interferon gamma(IFN-γ) and interleukin-2 (IL-2). MRI demonstrated detection of early superficial murine bladder tumour(MBT-2) and accurate sequential assessment of the topography and depth of intravesical tumour involvement.Response to intravesical instillations with multiple doses ofBRMs was assessed against early stageMBT-2 bladder tumours (confirmed by MRI) 14 days after transurethral tumour implantation. Serial MRIscans of TNF-α treated mice revealed significant retardation of tumour growth which correlated well withcorresponding histological examination of the whole mount bladder sections illustrating areas and depthof tumour regression. Intravesical instillation of combination TNF-α plus IFN-γ into tumour-bearing micecaused tumour growth inhibition up to 21 days following treatment; the results, however, were not superiorto those noted with TNF-α alone. Sequential MR images of tumour-bearing bladders following intravesicaltreatment with IL-2 revealed tumour regression with no visible tumour from day 21 to 33 post tumourimplant. Histological examination revealed foci of carcinoma in situ only. Control untreated bladdersrevealed deeply invasive transitional cell carcinoma. These results show that MRI offers a dependable toolfor noninvasive monitoring of tumour growth and of the course of experimental bladder tumour duringtherapy