Research ArticleCancer

In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma

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Science Translational Medicine  12 Jun 2019:
Vol. 11, Issue 496, eaat5857
DOI: 10.1126/scitranslmed.aat5857

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Zooming in on tumor cells

Circulating tumor cells in patients’ blood can offer insight into the underlying tumor and can also seed distant metastases. Thus, accurate detection of these cells could help with prediction of metastasis, as well as facilitate their elimination. Unfortunately, conventional methods of detection have limited sensitivity and can miss rare circulating tumor cells at an early, potentially treatable stage of disease. Galanzha et al. developed a photoacoustic method for use directly in patients with melanoma, allowing the researchers to detect very low numbers of circulating tumor cells in vivo, as well as destroy them with laser pulses, suggesting a therapeutic potential for this approach.

Abstract

Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the Cytophone technology using an in vivo photoacoustic flow cytometry platform with a high pulse rate laser and focused ultrasound transducers for label-free detection of melanin-bearing CTCs in patients with melanoma. The transcutaneous delivery of laser pulses via intact skin to a blood vessel results in the generation of acoustic waves from CTCs, which are amplified by vapor nanobubbles around intrinsic melanin nanoclusters. The time-resolved detection of acoustic waves using fast signal processing algorithms makes photoacoustic data tolerant to skin pigmentation and motion. No CTC-associated signals within established thresholds were identified in 19 healthy volunteers, but 27 of 28 patients with melanoma displayed signals consistent with single, clustered, and likely rolling CTCs. The detection limit ranged down to 1 CTC/liter of blood, which is ~1000 times better than in preexisting assays. The Cytophone could detect individual CTCs at a concentration of ≥1 CTC/ml in 20 s and could also identify clots and CTC-clot emboli. The in vivo results were verified with six ex vivo methods. These data suggest the potential of in vivo blood testing with the Cytophone for early melanoma screening, assessment of disease recurrence, and monitoring of the physical destruction of CTCs through real-time CTC counting.

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