Establishment of evaluating system for the efficacy of the prostate cancer gene therapy using orthotopic mouse tumor model

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The mouse orthotopic prostate tumor model has been recognized as an ideal preclinical animal model simulating the anatomical and biological milieu of the prostate. In comparison with the subcutaneous tumor model, the only disadvantage of this model is the difficulty of chronological tumor growth monitoring. We have applied the resent endoluminal ultrasound technology, transrectal ultrasonography (TRUS), to monitoring of mouse orthotopic prostate tumors.METHODS : A6 Fr. 20MHz catheter-based radial scan probe was used and TRUS was performed without any prior preparation including anesthesia. Orthotopic tumors were initiated by inoculation of 5000 RM-9 cells (provided by Dr.Thompson) into the dorsal prostate of 12-week-old C57/B6 male mice. The tumor growth was monitored by TRUS from Day 3 to Day 21. In addition, TRUS was performed to detect tumor growth suppression after intraperitoneal administration of cis-diamminedichloroplatinum (CDDP).RESULTS : Ultrasonically, tumors became detectable 7 days after tumor cell inoculation. TRUS images were clear and parallel to actual tumor growth. The estimated tumor volume (X) calculated by TRUS correlated significantly with the actual tumor weight (Y) measured at autopsy ; Y=101.653+1.174X (R=0.930, P<0.001). Similarly, tumor growth suppression induced by CDDP was clearly detected with reasonable accuracy.CONCLUSIONS : A high resolution TRUS allows simple and reliable monitoring of in situ tumor growth and growth suppression, making the mouse orthotopic prostate tumor model more efficient.