Dataset Information

Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin ?_v?₆.

ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. Today, cSCC is diagnosed by visual inspection followed by invasive skin biopsy. There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection. Photoacoustic imaging (PAI) possesses high ultrasonic resolution and strong optical contrast at new depths (<1-5?cm). Together with exogenous contrast agents, PAI has found promising use in various tumors in living subjects. The expression of integrin ?_v?₆ is significantly up-regulated in cSCC. We fabricated an anti-integrin ?_v?₆ antibody and labeled it with indocyanine green (ICG) to form an ICG-?_v?₆ antibody. The results showed that the ICG-?_v?₆ antibody probe could be used to detect cSCC with high specificity (3-fold over the control by PAI) and deep penetration (approximately 1?cm) by PAI. This suggests that the ICG-?_v?₆ antibody is a promising probe targeting the integrin ?_v?₆ for detection of cSCC tumors by PAI and fluorescence imaging. It may find clinical application in the early diagnosis of cSCC as well as in intraoperative navigation.

SUBMITTER: Zhang C

PROVIDER: S-EPMC5299425 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin α<sub>v</sub>β<sub>6</sub>.

Zhang Chao C Zhang Yong Y Hong Kai K Zhu Shu S Wan Jie J

Scientific reports 20170209

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. Today, cSCC is diagnosed by visual inspection followed by invasive skin biopsy. There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection. Photoacoustic imaging (PAI) possesses high ultrasonic resolution and strong optical contrast at new depths (<1-5 cm). Together with exogenous contrast agents, PAI has found promising use in various tumors in living subj ...[more]

PMID: 28181579

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Project description:Photoacoustic imaging is a nonionizing biomedical imaging modality with higher resolution and imaging depth than fluorescence imaging, which has greater sensitivity. The combination of the 2 imaging modalities could improve the detection of cancer. Integrin αvβ6 is a cell surface marker overexpressed in many different cancers. Here, we report the development and evaluation of a dye-labeled cystine knot peptide, which selectively recognizes integrin αvβ6 with high affinity, for photoacoustic and fluorescence imaging. The new dual-modality probe may find clinical application in cancer diagnosis and intraoperative imaging of integrin αvβ6-positive tumors.MethodsAn engineered cystine knot peptide, R01, that recognizes integrin αvβ6 was labeled with Atto 740 (A740) and evaluated for its specific cell uptake and its sensitivity threshold. A740-R01 was injected via the tail vein into nude mice xenografted with A431 (integrin αvβ6-positive) or 293T (integrin αvβ6-negative) tumors. Photoacoustic and fluorescence scans of tumors were acquired before and at 0.5, 1, 2, and 4 h after injection of A740-R01. Dynamic photoacoustic scans of various normal organs were also acquired. Ex vivo fluorescence imaging of tissues was performed 1 h after injection.ResultsThe A740-R01 demonstrated integrin αvβ6-dependent binding to A431 cells in culture. Sensitivity studies indicated that the probe may potentially detect lesions as small as 1 or 6 mm3 by fluorescence or photoacoustic imaging, respectively. The photoacoustic and fluorescence signals of A431 xenografts at 1 h after injection were 1.87 ± 0.25 arbitrary units (AU) and 8.27 ± 0.87 AU, respectively. Target specificity was confirmed by low tumor uptake in 293T tumors at 1 h after injection (1.07 ± 0.15 AU and 1.10 ± 0.14 AU for photoacoustic and fluorescence signals, respectively). A740-R01 exhibited hepatobiliary clearance marked by high uptake in the liver, spleen, and intestine but low uptake in the kidneys.ConclusionA740-R01 specifically targeted integrin αvβ6 with low nanomolar affinity. A740-R01 was able to detect integrin αvβ6 both in vitro and in vivo by photoacoustic and fluorescence imaging. A740-R01 is able to detect αvβ6-positive tumors in living subjects and may have clinical application in cancer diagnosis and real-time image-guided surgery.

Dataset Information

Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin ?v?6.

Publications

Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin α<sub>v</sub>β<sub>6</sub>.

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Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin ?_v?₆.