Pharmacokinetic Evaluation in Kras/p53 PDAC Mice

• Detailed pathology assessment of H&E-stained tissues at endpoint.
• Takes about five months to complete.
•  The Laboratory Animal Sciences Program will provide a full toxicity report and a collection of H&E stained tissue sections (one slide per tissue block).
• Includes sufficient basic consultation with a subject matter expert is included with the service.

Process

• Breed 24 KPC mice will be bred with the intent of generating a cohort of 18 animals with confirmed tumor-load matching the following enrollment criteria:
  • Female mice are considered eligible for enrollment when ultrasound examination within 24 hours reveals 1 or 2 tumors, with the largest size being 6–11 mm and a combined tumor volume of 100–350 mm3.
  • Animals with three or more tumors per organ; cystic tumors; signs of intestinal, pancreatic, or gall bladder duct occlusions; or otherwise moribund/showing signs of dilapidation will not be included in the study.
• Upon a single-dose injection, collect bleeds and biopsies of pre-specified tissue at five specified times (see Table A or B) after drug administration, processing three mice per each time point.
• Include three vehicle-treated mice that are processed for blood and tissue collection at the last time point as drug-naïve controls. 
• Provide cryopreserved plasma samples and tissues from PDAC tumor, lung, liver, and skeletal muscle for quantification of experimental compounds/metabolites.