SNMMI 2014: Circulating cancer cells count down to metastasis

ST. LOUIS—High-powered radioluminescence microscopy can home in on extremely scarce malignant cells among billions of normal cells in just 7.5 milliliters of blood. Leveraging the molecular imaging of circulating tumor cells (CTCs) could mean early detection of metastasis and the potential to improve survival for patients with several varieties of cancer, according to a study presented today during the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2014 Annual Meeting press conference.

SNMMI projects that metastasis accounts for about 90 percent of cancer deaths. Apparently CTC have been the subject of research since the late 1890s, but no one has been able to apply it to translational medicine. The technique presented by this study combines not only radioluminescence microscopy, which combines nuclear medicine and optical imaging, but also single-cell autoradiography (SCAR). This methodology is applied for localization of radioactivity micro-distribution in individual cells for the imaging of specific functions. Examples of these include enzymatic cellular metabolism or selected receptor expression.

“Researchers have shown that CTC can be shed from the patient’s primary tumor or from the patient’s metastases. Therefore, CTCs might be the biomarkers that are the most representative of a patient’s disease as a whole,” said Laura S. Sasportas, a PhD candidate in the Gambhir Lab in the Department of Bioengineering at Stanford University in Stanford, Calif . “They could be ideal candidates for a real-time ‘liquid biopsy’ of the tumor. The characterization of the properties of CTCs is poised to offer valuable information for predicting and monitoring a patient’s response to therapy.”

In recent years researchers have begun to piece apart CTCs at the genomic, RNA transcriptomic and proteomic space, but this may be the first time that the focus is on the metabolomics of CTCs.

In a sample of blood from a breast cancer patient, there may be just a few hundred cancer cells. For this study, researchers isolated blood from preclinical models of breast cancer and imaged them using radioluminescence microscopy and SCAR with F-18 FDG. Results showed that fewer than three percent of CTCs indicated increased cellular metabolism when compared to the original cell line. It is still not known exactly if this is a biomarker for metastasis, aggressiveness of disease and chance of survival.

“Several clinical studies (conducted with the FDA-approved CellSearch CTC detection system) have shown that the number of CTCs detected in a patient’s blood sample is correlated with the patient’s chances of survival,” added Sasportas. “This demonstrates the utility of counting CTCs as a prognosis biomarker for many types of cancer.”

Nethertheless, still more research in larger clinical trials are needed to strengthen the theory.

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