LASP-03: Pharmacokinetics Evaluation in Kras/p53 Pancreatic Ductal Adenocarcinoma (PDAC) Mice

The Laboratory Animal Sciences Program will 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, bleeds and biopsies of pre-specified tissue will be collected at five specified times (see Table A or B) after drug administration, processing three mice per each time point. Three vehicle-treated mice will be included and processed for blood and tissue collection at the last time point as drug-naïve controls. Cryopreserved plasma samples and tissues from PDAC tumor, lung, liver, and skeletal muscle will be provided for quantification of experimental compounds/metabolites.   

This service will take about five months to complete, and 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). Sufficient basic consultation with a subject matter expert is included with the service.

Table A

Group

Treatment

Dose

Collection Time

1

AE1

TBD, PO

1 hr

3

2

AE1

TBD, PO

2 hr

3

3

AE1

TBD, PO

4 hr

3

4

AE1

TBD, PO

12 hr

3

5

AE1

TBD, PO

24 hr

3

6

Vehicle

TBD, PO

24 hr

3

 

Table B

Group

Treatment

Single Dose

Collection Time

n 

1

AS1

TBD, IV

1 hr

3

2

AS1

TBD, IV

1 d

3

3

AS1

TBD, IV

3 d

4

AS1

TBD, IV

5 d

5

AS1

TBD, IV

7 d

3

6

Vehicle

TBD, IV

7 d

3

TBD* - Dosing concentrations will be provided by the requestor prior to the study beginning.