Abstract 1455: In vivo circulating tumor cells in blood, lymph and cerebrospinal fluid: dynamic cross-correlations and amplification for cancer diagnosis.

Abstract

Abstract We introduced a new platform of multicolor multi-fluid in vivo flow cytometry for real-time ultrasensitive molecular detection and counting of circulating tumor cells (CTCs) and their subpopulations the blood, lymph and cerebrospinal fluid's (CSF) flows. To achieve these goals we integrated multicolor photoacoustic (PA), photothermal (PT) and fluorescent flow cytometry, and combined this technical platform with multiplex molecular targeting strategy using low-toxicity, gold-based functionalized nanoparticles as PA/PT high-contrast agents or genetically encoded proteins (e.g., green fluorescent protein [GFP]) as fluorescent labels. This platform can provide also label-free detection mode using intrinsic (e.g., melanin) molecular labels. The advantages of this new generation of flow cytometries are (1) improving sensitivity by at least a two-order of magnitude compared to available CTC-assays, and (2) significantly extending biomedical applications compared to existing in vivo flow cytometries. Using preclinical tumor-bearing mouse models of metastatic melanoma and breast cancer, and spiked human blood samples, we demonstrated that our technology can overcome great challenge in cancer research related to monitoring lymph, CSF and blood CTCs at single-cell levels in the natural environment in vivo over the long-term period of metastatic disease development from an early micrometastatic stage to deadly multiple macro-metastases. The obtained results allowed us to estimate in vivo cross-correlations between lymph, CSF and blood CTC counts, size of primary tumor and metastasis (micrometastasis) progression. We also showed that the presented approach can break some important diagnostic limitations of existing methods (e.g., low sensitivity) and potentially permits prevention, or at least inhibition, of metastatic progression. Taking into account the safe nature of the PA technology, we anticipate its quick translation for use in humans. Citation Format: Ekaterina I. Galanzha. In vivo circulating tumor cells in blood, lymph and cerebrospinal fluid: dynamic cross-correlations and amplification for cancer diagnosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1455. doi:10.1158/1538-7445.AM2013-1455 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.