HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.107.043216v1 48/11/1862    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cai, W. Articles by Chen, X. Search for Related Content PubMed PubMed Citation Articles by Cai, W. Articles by Chen, X.

Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature

¹ Molecular Imaging Program at Stanford (MIPS), Department of Radiology, and Bio-X Program, Stanford University School of Medicine, Stanford, California; and ² Department of Bioengineering, Stanford University School of Medicine, Stanford, California

Correspondence: For correspondence or reprints contact: Xiaoyuan Chen, PhD, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd., P095, Stanford, CA 94305-5484. E-mail: shawchen{at}stanford.edu

To date, the in vivo imaging of quantum dots (QDs) has been mostly qualitative or semiquantitative. The development of a dual-function PET/near-infrared fluorescence (NIRF) probe can allow for accurate assessment of the pharmacokinetics and tumor-targeting efficacy of QDs. Methods: A QD with an amine-functionalized surface was modified with RGD peptides and 1,4,7,10-tetraazacyclodocecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelators for integrin _vß₃–targeted PET/NIRF imaging. A cell-binding assay and fluorescence cell staining were performed with U87MG human glioblastoma cells (integrin _vß₃–positive). PET/NIRF imaging, tissue homogenate fluorescence measurement, and immunofluorescence staining were performed with U87MG tumor–bearing mice to quantify the probe uptake in the tumor and major organs. Results: There are about 90 RGD peptides per QD particle, and DOTA–QD–RGD exhibited integrin _vß₃–specific binding in cell cultures. The U87MG tumor uptake of ⁶⁴Cu-labeled DOTA–QD was less than 1 percentage injected dose per gram (%ID/g), significantly lower than that of ⁶⁴Cu-labeled DOTA–QD–RGD (2.2 ± 0.3 [mean ± SD] and 4.0 ± 1.0 %ID/g at 5 and 18 h after injection, respectively; n = 3). Taking into account all measurements, the liver-, spleen-, and kidney-to-muscle ratios for ⁶⁴Cu-labeled DOTA–QD–RGD were about 100:1, 40:1, and 1:1, respectively. On the basis of the PET results, the U87MG tumor-to-muscle ratios for DOTA–QD–RGD and DOTA–QD were about 4:1 and 1:1, respectively. Excellent linear correlation was obtained between the results measured by in vivo PET imaging and those measured by ex vivo NIRF imaging and tissue homogenate fluorescence (r² = 0.93). Histologic examination revealed that DOTA–QD–RGD targets primarily the tumor vasculature through an RGD–integrin _vß₃ interaction, with little extravasation. Conclusion: We quantitatively evaluated the tumor-targeting efficacy of a dual-function QD-based probe with PET and NIRF imaging. This dual-function probe has significantly reduced potential toxicity and overcomes the tissue penetration limitation of optical imaging, allowing for quantitative targeted imaging in deep tissue.

Key Words: dual-function probe • PET • near-infrared fluorescence • quantum dot • integrin _vß₃

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2007 48: 11A-12A. [Full Text]  

This article has been cited by other articles:

				S. Jiang, M. K. Gnanasammandhan, and Y. Zhang Optical imaging-guided cancer therapy with fluorescent nanoparticles J R Soc Interface, January 6, 2010; 7(42): 3 - 18. [Abstract] [Full Text] [PDF]

				J. L. Pelley, A. S. Daar, and M. A. Saner State of Academic Knowledge on Toxicity and Biological Fate of Quantum Dots Toxicol. Sci., December 1, 2009; 112(2): 276 - 296. [Abstract] [Full Text] [PDF]

				G. TING, C.-H. CHANG, and H.-E. WANG Cancer Nanotargeted Radiopharmaceuticals for Tumor Imaging and Therapy Anticancer Res, October 1, 2009; 29(10): 4107 - 4118. [Abstract] [Full Text] [PDF]

				L. A. Bentolila, Y. Ebenstein, and S. Weiss Quantum Dots for In Vivo Small-Animal Imaging J. Nucl. Med., April 1, 2009; 50(4): 493 - 496. [Abstract] [Full Text] [PDF]

				W. Cai and X. Chen Multimodality Molecular Imaging of Tumor Angiogenesis J. Nucl. Med., June 1, 2008; 49(Suppl_2): 113S - 128S. [Abstract] [Full Text] [PDF]