The Prostate 67:396 ^ 404 (2007) Magnetic Resonance Imaging and Histopathological Characterization of ProstateTumors inTRAMP Mice as Model for Pre-Clinical Trials Anna Degrassi, 1 * Micaela Russo, 1 Eugenio Scanziani, 2 Anna Giusti, 3 Roberta Ceruti, 1 Gemma Texido, 1 and Enrico Pesenti 1 1 Pharmacology Department, Nerviano Medical Sciences, Nerviano (MI), Italy 2 Department of Veterinary Pathology, Hygiene and Public Health,University of Milan, Milan, Italy 3 Preclinical Development Department, Nerviano Medical Sciences, Nerviano (MI), Italy BACKGROUND. The Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) develops progressive forms of prostate cancer. Due to the lack of a validated non-invasive methodology, pathology has been so far the most common parameter evaluated in efficacy studies. METHODS. We studied by magnetic resonance imaging (MRI) 210 mice that were repeatedly measured up to 33 weeks of age in order to stage prostate tumors and follow pathological progression in single animals. A pre-clinical trial with doxorubicin was also performed. RESULTS. Progressive forms of cancer (well and poorly differentiated (PD) adenocarcinomas) were easily recognized on MR images and MRI findings were validated against histopatho- logical analysis. Age at tumor onset was different for the two tumoral forms. Doxorubicin treatment caused a strong reduction in tumor volume. CONCLUSIONS. Prostate cancer in TRAMP mice is multifocal and heterogeneous: a non- invasive methodology such as MRI facilitates the rational design of translational pre-clinical trials in this widely used animal model. Prostate 67: 396 – 404, 2007. # 2006 Wiley-Liss, Inc. KEY WORDS: MRI; TRAMP; pre-clinical trials; doxorubicin INTRODUCTION Prostate cancer alone accounts for approximately 33% of all newly diagnosed cancers in men and is the second most common cause of cancer death among aged 80 and older [1]. Since it is a heterogeneous disease of a heterogeneous population [2], it has been difficult to progress significantly in the comprehension of the natural history of this disease and in finding new modalities for prevention and intervention. Hence, good animal models with defined genetic alterations that could recapitulate many of the changes seen in human cancer are needed. A number of groups have worked in the development and characterization of germ-line murine models that could closely mimic the progressive pathological and biochemical features of prostate cancer in man. In contrast to in vitro culture or orthotopic transplantation of human cell lines, these autochthonous murine models more closely mimic the complex sets of cellular, tissutal, and hormonal inter- actions that occur in a complex organ such as the pro- state. Although there may never be one perfect model, few good models are currently in use [3]. Among these, the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model of prostate cancer is probably the most used worldwide to identify molecular mechanisms contributing to the initiation and progression of pro- state cancer and to test chemoprevention strategies and therapies. In the TRAMP model, the rat prostate-specific promoter probasin directs expression of the SV40 early genes (T and t antigen) to the prostate epithelium lead- ing to cell transformation through abrogation of p53, *Correspondence to: Dr. Anna Degrassi, Pharmacology Department, Nerviano Medical Sciences, v.le Pasteur 10, Nerviano, Milano, Italy. E-mail: Anna.Degrassi@nervianoms.com Received 31 May 2006; Accepted 31 July 2006 DOI 10.1002/pros.20511 Published online 22 December 2006 in Wiley InterScience (www.interscience.wiley.com). ß 2006 Wiley-Liss, Inc.