RT Journal Article
SR Electronic
T1 A Cystine Knot Peptide Targeting Integrin α<sub>v</sub>β<sub>6</sub> for Photoacoustic and Fluorescence Imaging of Tumors in Living Subjects
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1629
OP 1634
DO 10.2967/jnumed.115.169383
VO 57
IS 10
A1 Zhang, Chao
A1 Kimura, Richard
A1 Abou-Elkacem, Lotfi
A1 Levi, Jelena
A1 Xu, Lingyun
A1 Gambhir, Sanjiv Sam
YR 2016
UL http://jnm.snmjournals.org/content/57/10/1629.abstract
AB 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. Methods: An 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. Results: The 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. Conclusion: A740-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.