The main advantages of BLI is sensitivity: Background is virtually absent in mammals imaged in light-tight specimen chambers attached to cryogenically cooled (РІвЂ°В¤РІв‚¬вЂ™105РІВРЉ) CCD cameras. Alternatively, advances in charged coupled devices (CCD) have made optical imaging quite feasible for both fluorescence and especially bioluminescence imaging (BLI), where typically the oxidation of d-luciferin is observed following the Mg-ATP- and O 2-dependent catalysis by firefly luciferase ( 6). A new three-dimensional ultrasound microimaging technology has been developed with very good spatial resolution at low cost that has been used to image spontaneous models of prostate cancer ( 5).

Molecular imaging using positron emission tomography (PET) and techniques based on detection of РћС–-rays produced by radiolabeled probes can provide resolution near 1 to 2 mm, but these methods require expensive equipment and relatively slow throughput. The highest spatial resolution is obtained with magnetic resonance imaging and computed tomography that can get close to 25 РћСm with long (>15 minutes) scan times. (Cancer Res 2006 66(12): 6199-209)Р”Р„pproaches to noninvasive imaging differ by a number of key variables, such as spatial resolution, depth, imaging times, sensitivity, type of probe, cost, and others (reviewed in ref. These models also provide powerful new reagents for developing improved drugs that inhibit the AR axis. The EZC-prostate model permits prostate imaging in vivo and should be useful for imaging prostate development, growth, metastasis, and response to treatment noninvasively and longitudinally. Castration reduced luciferase expression by 90% and 97% in EZC2 and EZC3 mice, respectively, and use of GnRH antagonist also led to extensive inhibition of reporter activity. When crossed with prostate cancer models, EZC3 facilitated detection of metastatic lesions although total prostate luciferase expression was static or reduced due to weakening of AR-regulated promoters.

To image prostate cancer progression, lines of EZC mice were bred with prostate cancer models TRAMP and JOCK1, and imaged longitudinally. Luciferase expression was detected as early as embryonic day 13 (E13) in the urogenital track. EZC2 and EZC3-prostate display robust expression in the prostate with only minimal detectable expression in other organs, including testes and epididymis. A luciferase reporter gene was directed to the prostate epithelium using three composite promoters called human kallikrein 2 (hK2)-E3/P, PSA-E2/P, and ARR 2PB, derived from hK2, PSA, and rat probasin regulatory elements, to generate the EZC1, EZC2, and EZC3-prostate mice, respectively. Further, we show the use of these models for detecting small metastasis and testing reagents that modulate the androgen receptor (AR) axis.

Herein, we describe two new models that permit prostate imaging ex vivo, in vivo, and in utero. In vivo imaging advances have greatly expanded the use of animal cancer models.

Image pro plus pseudocolor h&e