Preclinical Therapeutics

Cell and tissue engraftment

• The PTC has expertise in high volume cell culture, and maintains a large cryorepository of commonly used tumor cell lines and tissues
• Xenografts or allografts are generated via cell and/or tissue implantation; as well as orthotopic engraftment

Compound formulation and delivery

• The PTC has expertise in formulating experimental agents for delivery using a variety of commonly used methods (i.e. oral gavage, intra-peritoneal, intra-venous by tail vein, hydrodynamic, intra-tumoral, subcutaneous and osmotic mini-pumps)

Animal monitoring and tissue collection

• The PTC monitors animal welfare by serial body weight and tumor measurement using digital calipers and balances
• In vivo imaging is also used to assess tumor size, location and dissemination, including μCT and ultrasound imaging, as well as IVIS imaging of bioluminescent or fluorescently labelled tumors
• PTC performs collection of body fluids (including blood and urine), tissues and tumors as needed per experimental design. Standard tissue processing includes fixation for paraffin/OCT embedding, snap-freezing, and cryopreservation

Pharmacokinetic (PK) and pharmacodynamic (PD) analysis

• The Core assists users in their PD and PK studies
• For PK analysis, after single or multi-day delivery of experimental agent, plasma/serum is collected at multiple time points over a 24-72 hr period for assessment of drug persistency (note: analyte determination done by user)
• For PD analysis, mice are typically treated with an experimental agent for 3-5 days before tissue/tumor is collected for molecular target analysis or biodistribution

Patient derived tumor xenografting

• The Core engrafts fresh human tumor tissue derived from patient biopsy or surgery into immunodeficient mice
• Tumor tissue that grows in vivo is propagated by surgical removal, dissection into fragments, and reimplantation into host mice, and samples are cryopreserved and banked for subsequent in vivo implantation and experimental use

Models of metastatic disease

• The PTC generates new and established models of metastatic disease. In most cases, molecular imaging methods allow evaluation of tumor location and overall tumor burden, including metastases

Surgical procedure training

• The PTC in collaboration with LARC has developed a program of certified training for survival surgery procedures
• The PTC provides both 1:1 session and hands-on training in addition to assist students and research fellows who need to learn surgical procedures

The PTC oversees and provides access and user training for multiple small animal imaging devices housed within the barrier facilities at Mission Bay (HD527,HD537,HD538), Mount Zion (S0171) and Parnassus (PSB554) campuses.

Vevo 2100 (HD527) and Vevo 770 (PSB554) High Frequency Ultrasound

Image

• Visualization and quantification of small animal anatomical targets in tandem with hemodynamic evaluation with resolution as low as 30 microns
• Non-invasive, non-radioactive, therapeutic regimes can be monitored in the same animal over time
• Power Doppler mode allows for blood flow quantification & anatomical identification
• 3D Imaging & Volume Analysis
• Contrast enhanced imaging and quantification
• Presence of molecular biomarkers
• Not applicable for brain or lung imaging

Xenogen IVIS Spectrum Fluorescent and Bioluminescent Imager (HD538, PSB554, S071)

• Quantitative imaging of bioluminescent or fluorescent tumor cells/probes within small live animal models
• Multispectral fluorescent imaging options
• Dual illumination capability enables topographic localization of both shallow and deep tumors in 3-D and reduces background interference.
• 20µM Resolution at 3.9cM field width

Small Animal Radiation Research Platform (SARRP) uCT-guided Precision Irradiator (HD-537)

• SARRP delivers targeted radiation to pre-clinical animal models with an accuracy equivalent to clinical radiotherapy
• Using on-board high resolution 3-D cone beam-Computed Tomography (CT) imaging, the SARRP can target micro beams (down to 0.5mm) of radiation achieving an accuracy of 200um for irradiated target
• SARRP software allows user to image animal, contour the tumor/target and at risk organs, evaluate dose, and deliver the desired treatment

Quantum G2X uCT (HD538)

• High resolution (2.3 uM voxel size)
• High-speed (scans as fast as 3.9 seconds)
• Low-dose imaging for longitudinal in vivo studies
• Four Field of Views (FOVs) –18, 36, 72, and 86mm
• Multispecies imaging capabilities (Zebrafish/mouse/rat/guinea pig/rabbit) Two-phase retrospective respiratory and cardiac gating, ideal for imaging heart and lungs Seamless co-registration of functional optical signals (from IVIS® Spectrum or FMT®) with microCT imaging data

Additional Resources
A searchable database of core facilities at all UCSF campus locations is available here.