Validation of transrectal ultrasonographic volumetry for orthotopic prostate tumours in mice

Abstract

Orthotopic human prostate tumour models in athymic nude mice are regarded as being most suitable for fundamental and pre-clinical research on prostate cancer. The anatomic localization of the tumour in the pelvis, however, provides little possibility for monitoring tumour growth or regression. To assess time-related changes in orthotopic tumour volume, we applied transrectal ultrasonography (TRUS) to the murine prostate. This technique has the advantages of allowing accurate monitoring of tumours during therapeutic manipulations and a reduction of animal use due to a reduction of sacrificing endpoints. To validate the TRUS method, the mouse prostate reconstitution model, RM-9, and the prostate-specific antigen (PSA) producing human prostate cancer xenograft PC-346 were used. Volumetric calliper measurements were performed with a 30 MHz ultrasound probe designed for intra-arterial use in humans. Tumour weight, determined at various time-points, was found to be closely related to actual tumour weight (R = 0.99) and, in the PC-346 model, to the level of PSA in the plasma. Furthermore, the interobserver variation for TRUS was low for tumours above 50 mg. Thus, TRUS for murine prostate tumours proves to be an accurate, reproducible and sensitive method.

Disconnecting the Yin and Yang Relation of Epidermal Growth Factor Receptor (EGFR)-Mediated Delivery: A Fully Synthetic, EGFR-Targeted Gene Transfer System Avoiding Receptor Activation

“…Mice were kept in individually ventilated cages (Tecniplast, Buguggiate, Italy) under a 12-hr light/ dark cycle and received irradiated chow and acidified drinking water ad libitum. Orthotopic tumor growth was monitored over time by transrectal ultrasonography of the mouse prostate (Kraaij et al, 2002). When tumors reached a size of 50-100 mm 3 (15-20 days after inoculation), polyplexes formed with the luciferase reporter plasmid pCpG-hCMVLuc were injected directly into the prostate tumor tissue at a concentration of 200 lg/ml in a total volume of 50 ll.…”

Validation of Ultrasonography to Evaluate Murine Orthotopic Oral Cavity Tumors

“…Invasive procedures to evaluate tumor size require exposing the animal to infection and possibly altering the tumor microenvironment. Ultrasound has been used with success in the murine orthotopic prostate tumor model [3,6] . In these prostate murine models the ultrasound evaluation of tumors was found to correlate with wet weight and histology [3,6] .…”

“…Ultrasound has been used with success in the murine orthotopic prostate tumor model [3,6] . In these prostate murine models the ultrasound evaluation of tumors was found to correlate with wet weight and histology [3,6] . Ultrasound was applied to evaluate murine orthotopic oral cavity tumors as compared to conventional sacrifi ce with conventional histological sectioning.…”

Human xenograft models as useful tools to assess the potential of novel therapeutics in prostate cancer

“…In the case of PSA-producing cells, plasma PSA may be used as an indicator of tumour burden, although this approach would lack validation of circulating PSA levels to actual tumour load (Thalmann et al, 1996). To allow longitudinal studies in individual mice to evaluate treatment efficacy, a three-dimensional ultrasound micro-imaging technique was developed that allows us to frequently monitor prostate (tumour) volume (Kraaij et al, 2002). For many years, this micro-imaging technique using transrectal ultrasonography is a validated and routine procedure to monitor prostate volume in all our orthotopic studies (Figure 1).…”

“…Figure 1 Transrectal ultrasonography to monitor orthotopic tumour growth in the mouse prostate. PC346C human prostate cancer cells were injected into the dorsolateral lobe of the mouse prostate and prostate volume was imaged longitudinally Kraaij et al (2002).…”