Abstract 1977: Tracking cancer colonization in xenografts using ultrasensitive accelerator mass spectrometry methods

Background: The inability to effectively treat metastases is the main reason for the limited progress in reducing the rates of cancer morbidity and mortality. One major drawback is the lack of quantitative assays for assessing the size and tissue prevalence of tumors in newly diagnosed individuals. Current methods for quantifying tumor burden are mainly qualitative and include measuring the gross weight of the affected organ, counting tumors on the surface of the organ, or evaluating a small sample of the organ using histologic sections. These methods are crude measures of tumor burden and size distribution, and in the case of histology, they are time consuming, difficult to process an adequate sample size and non-quantitative. Methods: Animal models of metastasis have been useful in identifying genes that regulate susceptibility to the development and progression of metastasis and have helped to highlight potential novel targets for drug development. In particular several small animal imaging technologies including magnetic resonance imaging, high frequency ultrasound, and optical imaging have been recently applied to this task. Each of these methods may be useful for specific research projects, based on their unique combination of resolution, image acquisition time, animal throughput, and cost-effectiveness, yet none of these modalities adequately address the need for rapid quantification of tumors across the entire organism, nor do they assess therapeutic effectiveness in eradicating cancer in xenograft models. We have developed an Accelerator Mass Spectrometry (AMS)-based high precision quantitative method for assessing the metastatic potential of primary tumors isolated from newly diagnosed patients. Results: Our AMS-based methodology to study metastasis uses xenograft cancer cells labeled with 14 C-labeled thymidine that are delivered intravenously into NSG mice and allowed to develop metastatic cancer over the course of up to 10 weeks. At the end of the experiment, all vital organs are collected; the DNA is isolated and is examined by AMS for the presence of 14 C-signal. The labeling was optimized to achieve sufficient signal such that a tumor derived from a single cell could be detected by AMS, in secondary tumors, in vivo, independent of histological data. Conclusions: Using this approach we have determined that tissue colonization by tumor cells is a very rare event, where most metastatic tumors are initiated by less than 10 cells delivered into NSG mice. Further optimization of these techniques will allow us to explore the metastatic potential of primary tumors, isolated from biopsies and expanded in Avatar mice. This study was supported in part by NIH P41MI03483 and was conducted under the auspices of the USDOE by LLNL (DE-AC52-07NA27344). IM number: LLNL-678306 Citation Format: Nicholas R. Hum, Kelly A. Martin, Michael Malfatti, Kurt Haack, Bruce A. Buchholz, Gabriela G. Loots. Tracking cancer colonization in xenografts using ultrasensitive accelerator mass spectrometry methods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1977. doi:10.1158/1538-7445.AM2017-1977