Summary

Pre-clinical animal models of spontaneous metastatic cancer are infrequent; the few that exist are resource intensive because determination of the presence of metastatic disease, metastatic burden, and response to therapy normally require multiple timed cohorts with animal sacrifice and extensive pathological examination. We identified and characterized a patient derived xenograft model with metastatic potential, adenocarcinoma pancreas xenograft 521955-158-R4. In this study we performed a detailed imaging characterization (workflow below) of this model, which develops spontaneous lung metastases, details are provided in the attached standard operating procedures. Tumors in half of the mice were resected in the range 200-300 mm³ size; tumors in the other half were allowed to grow until it was necessary to euthanize them because of tumor size.

The imaging characteristics of this model (PDMR-521955-158-R4), which is available from the National Cancer Institute Patient-Derived Models Repository (https://pdmr.cancer.gov/), is highly favorable for preclinical research studies of metastatic disease when used in conjunction with non-contrast T2 weighted MRI.

Results: Adenocarcinoma pancreas (PDMR-521955-158-R4)

Table 1: Penetrance and location of pathological confirmed metastatic lesion(s).

Percent penetrance with respect to the average time-to-metastasis for non-resected (time from implant: 10.7 ± 1.8 weeks) and resected (time from tumor resection: 5.3 ± 1.1 weeks) cohorts.

PET/CT Characterization of the primary tumor:  Baseline PET (SOP attached) were performed when tumor reached an approximate 200 mm³.   Average SUVmax values (n=6) were calculated; [¹⁸F]FDG: 2.3 ± 0.8 and [¹⁸F]FLT: 2.4 ± 0.4.

Conclusion:

Good metastatic model with 40% penetrance un-resected and 70% with planned early resection.  Metastases are well observed on T2 MRI imaging allowing non-invasive evaluation in treatment trials.