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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 animal sacrifice and extensive pathological examination. We identified and characterized a patient derived xenograft model with metastatic potential, melanoma xenograft 425362-245-T. In this study we performed a detailed imaging characterization of this model, which develops spontaneous lung metastases. Twenty (20) female NSG mice were implanted on the right flank on 07/22/2019. Mice were then randomized into two groups of ten (10 mice); resected and non-resected. All mice in the resected group had xenograft resected on the same day in a tumor volume range of 200 – 300 mm3. MRI imaging sessions were performed bi-weekly on 8/29/2019 (baseline), and six (6) biweekly sessions ending 12/05/2019. [18F]FDG (6.2 ± 0.5 MBq injected) and [18F]FLT (5.7 ± 0.8 MBq injected) PET/CT imaging was performed at baseline (prior to tumor excision) on 8/21/2019. PDMR reported mutations: BRAF V600E, PTEN, H259Y, TP53 C2777Y

Non-resected Group: Six (6) of ten (10) mice required protocol directed EU due to size of xenograft prior to imaging evidence of metastatic disease. The remaining four (4) mice all developed pathology confirmed metastatic disease to the lungs. Time to metastatic disease on MRI averaged 84 days with a range of 52-102 days post implantation. Resected Group: Ten (10) mice that underwent planned xenograft resection all developed MRI imaging findings of pulmonary and renal metastasis (100% penetrance) at an average of 107 days post xenograft implantation (range 80 – 136 days) and an average 56 days (range 36 – 92 days) post resection. Pulmonary and renal metastasis was confirmed by PHL in all 10 mice. Conclusion: Melanoma PDMR-425362-245-T model can be challenging due to the rapid growth of the xenograft and regrowth. Metastases was well observed on T2 MRI imaging allowing non-invasive evaluation in treatment trials. Baseline PET [18F]FDG SUVmax: 2.7 ± 0.5 Baseline PET [18F]FLT SUVmax: 2.0 ± 0.3


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Acknowledgement

This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201500003I. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

TCIA Citation

Clark K, Vendt B, Smith K, Freymann J, Kirby J, Koppel P, Moore S, Phillips S, Maffitt D, Pringle M, Tarbox L, Prior F. The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository, Journal of Digital Imaging, Volume 26, Number 6, December, 2013, pp 1045-1057. DOI: https://doi.org/10.1007/s10278-013-9622-7

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