Background:
Most small animal experimental models for anti-tumor therapy rely on crude tumor size measurements and necropsy results and suffer from the inability to monitor treatment progress or tumour kinetics as well as inability to confirm the presence of non-palpable tumors. Herein we describe a 3-dimensional ultrasound (3D US) micro-imaging system with an orthotopic transgenic mouse model designed to circumvent these problems.
Methods:
A 3.84 kb promoter/enhancer region of the PSP-94 gene directing SV40 T/t antigen targeted specifically to mouse prostate tissue and strain F1 (C57BL/6 x CBA) mice were used to establish the PSP94 gene-directed transgenic mouse orthotopic adenocarcinoma of prosztate (TGMAP) model. Serial US was performed using a micro imaging system (Vevo 660, VisualSonics Inc Toronto Canada) with 3D image reconstruction utilizing software developed at our laboratory.The micro- imaging was performed weekly. 3-D reconstruction of serial H&E stained histologic slides were taken from selected animals sacrificed for qualitative comparison and confirmation of ultrasound images. Slides at 50 um spacing were digitized at 10X modification using a video microscopy system. Tumor diameter, volume and growth curve measurements were derived from 3-D image analysis software compared with physical measurements.
Results:
Forty-five transgenic mice were imaged a total of 278 times. The US imaging had a diagnostic sensitivity of 93% and specificity of 100%. 3-D reconstruction imaging compared with serial histologic section showed high fidelity with the US images in terms of size, shape and configuration of tumors as well as the relative location of adjacent organs and peri-prostatic tissues. Regional lymph node metastasis was also identified and confirmed. Tumor diameter growth curve from gross pathology and ultrasound imaging showed agreement in 2 mice at r = 0.986 versus 0.980 and 0.939 versus 0.943 respectively.
Conclusions:
This non-invasive micro imaging system which permits serial imaging of orthotopic prostate cancer in a transgenic mouse system has numerous advantages including accurate serial monitoring of treatment response, growth curve measurements and tumor kinetics while minmizing the number of experimental subjects and the associated costs. High spatial resolution was feasible allowing detection of changes in measurements of small early-staged tumors. This model is a valuable tool for experimental therapeutic trials in prostate cancer.

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