Abstract
.Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention.Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs.Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans.Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR . CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression.Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.
Highlights
More than 90% of cancer-associated mortality is caused by metastasis,[1] the process of cancer cells spreading from a primary tumor site to surrounding tissues and distant organs to form new tumors
It is constrained by the limited blood sample volume in ex vivo assays relative to the patient’s entire blood volume, which reduces the sensitivity of circulating tumor cells (CTCs) detection
3.1 linear-array-based photoacoustic tomography system (LA-photoacoustic tomography (PAT)) of Melanoma Tumor Cells in Phantoms To initially demonstrate the capability of LA-PAT, we first applied it to image melanoma tumor cells in tissue-mimicking phantoms
Summary
More than 90% of cancer-associated mortality is caused by metastasis,[1] the process of cancer cells spreading from a primary tumor site to surrounding tissues and distant organs to form new tumors. To improve the detection sensitivity, in vivo optical CTC imaging techniques have been developed,[10] including in vivo fluorescent flow cytometry,[11] in vivo photoacoustic flow cytometry,[12] and multiphoton microscopy.[13] most of these techniques require labeling CTCs by transfection, and their clinical translation is impeded by low in vivo transfection efficiency as well as the potential toxicity of labeled CTCs. because of strong optical scattering in biological tissue, prior noninvasive optical CTC imaging methods rely on imaging special anatomical sites, such as the mouse ear.[12] Sites with similar optical properties may not be readily available for human studies. A new imaging method that can monitor metastasis using endogenous contrast over a long duration at an arbitrary anatomical location is desirable
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