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

Abstract

The authors evaluated magnetic resonance imaging (MRI) for monitoring orthotopic bladder tumour growth 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 stage MBT-2 bladder tumours (confirmed by MRI) 14 days after transurethral tumour implantation. Serial MRI scans of TNF-α treated mice revealed significant retardation of tumour growth which correlated well with corresponding histological examination of the whole mount bladder sections illustrating areas and depth of tumour regression. Intravesical instillation of combination TNF-α plus IFN-γ into tumour-bearing mice caused tumour growth inhibition up to 21 days following treatment; the results, however, were not superior to those noted with TNF-α alone. Sequential MR images of tumour-bearing bladders following intravesical treatment with IL-2 revealed tumour regression with no visible tumour from day 21 to 33 post tumour implant. Histological examination revealed foci of carcinoma in situ only. Control untreated bladders revealed deeply invasive transitional cell carcinoma. These results show that MRI offers a dependable tool for noninvasive monitoring of tumour growth and of the course of experimental bladder tumour during therapy.