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 alpha(v)beta(6) 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 alpha(v)beta(6) 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 alpha(v)beta(6) positive tumors. Methods: An engineered cystine knot peptide, R(0)1, that recognizes integrin alpha(v)beta(6) was labeled with Atto 740 (A740) and evaluated for its specific cell uptake and its sensitivity threshold. A740-R(0)1 was injected via the tail vein into nude mice xenografted with A431 (integrin alpha(v)beta(6)-positive) or 293T (integrin alpha(v)beta(6) 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. Results: The A740-R01 demonstrated integrin alpha(v)beta(6) dependent binding to A431 cells in culture. Sensitivity studies indicated that the probe may potentially detect lesions as small as 1 or 6 mm(3) 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. Conclusion: A740-R01 specifically targeted integrin alpha(v)beta(6) with low nanomolar affinity. A740-R01 was able to detect integrin a,(36 both in vitro and in vivo by photoacoustic and fluorescence imaging. A740-R01 is able to detect alpha(v)beta(6)-positive tumors in living subjects and may have clinical application in cancer diagnosis and real-time image-guided surgery.
基金：
NCI ICMIC [P50CA114747]; Canary Foundation; Ben & Catherine Ivy Foundation; Sir Peter Michael Foundation
第一作者单位：[1]Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Canary Ctr Canc Early Detect, Stanford, CA 94305 USA[2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Med Ultrasound, Wuhan, Peoples R China
通讯作者：
通讯机构：[1]Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Canary Ctr Canc Early Detect, Stanford, CA 94305 USA[*1]James H Clark Ctr, Mol Imaging Program Stanford, 318 Campus Dr, Stanford, CA 94305 USA
推荐引用方式(GB/T 7714)：
Zhang Chao,Kimura Richard,Abou-Elkacem Lotfi,et al.A Cystine Knot Peptide Targeting Integrin αvβ6 for Photoacoustic and Fluorescence Imaging of Tumors in Living Subjects[J].JOURNAL OF NUCLEAR MEDICINE.2016,57(10):1629-1634.doi:10.2967/jnumed.115.169383.
APA：
Zhang, Chao,Kimura, Richard,Abou-Elkacem, Lotfi,Levi, Jelena,Xu, Lingyun&Gambhir, Sanjiv Sam.(2016).A Cystine Knot Peptide Targeting Integrin αvβ6 for Photoacoustic and Fluorescence Imaging of Tumors in Living Subjects.JOURNAL OF NUCLEAR MEDICINE,57,(10)
MLA：
Zhang, Chao,et al."A Cystine Knot Peptide Targeting Integrin αvβ6 for Photoacoustic and Fluorescence Imaging of Tumors in Living Subjects".JOURNAL OF NUCLEAR MEDICINE 57..10(2016):1629-1634
医学