HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH 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.108.051243v1 49/8/1371    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 Google Scholar Articles by Lee, H.-Y. Articles by Chen, X. PubMed PubMed Citation Articles by Lee, H.-Y. Articles by Chen, X.

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

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 Chemistry, Brown University, Providence, Rhode Island

Correspondence: For correspondence or reprints contact: Xiaoyuan Chen, 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

The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for PET and MRI scans of tumor integrin _vβ₃ expression. Methods: Polyaspartic acid (PASP)–coated IO (PASP-IO) nanoparticles were synthesized using a coprecipitation method, and particle size and magnetic properties were measured. A phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for integrin _vβ₃ targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N'',N''',-tetraacetic acid (DOTA) chelators for PET after labeling with ⁶⁴Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to determine receptor targeting efficacy and feasibility for dual PET/MRI. Results: PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with a hydrodynamic diameter of 45 ± 10 nm. The saturation magnetization of PASP-IO nanoparticles is about 117 emu/g of iron, and the measured r₂ and r₂* are 105.5 and 165.5 (s·mM)^–1, respectively. A displacement competitive binding assay indicates that DOTA-IO-RGD conjugates bound specifically to integrin _vβ₃ in vitro. Both small-animal PET and T2-weighted MRI show integrin-specific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system uptake. Conclusion: We have successfully developed an IO-based nanoprobe for simultaneous dual PET and MRI of tumor integrin expression. The success of this bifunctional imaging approach may allow for earlier tumor detection with a high degree of accuracy and provide further insight into the molecular mechanisms of cancer.

Key Words: PET • MRI • iron oxide nanoparticle • RGD peptide • bifunctional probe • integrin _vβ₃

^* Contributed equally to this work.

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2008 49: 11A-12A. [Full Text]