Theranostics 2012; 2(8):746-756. doi:10.7150/thno.4762

Research Paper

Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe

Lei Zhu1,2,*, Ning Guo2,3,*, Quanzheng Li4, Ying Ma2, Orit Jacboson2, Seulki Lee2, Hak Soo Choi5, James R. Mansfield6, Gang Niu2✉, Xiaoyuan Chen2✉

1. Center for Molecular Imaging and Translational Medicine, Xiamen University, Xiamen, Fujian, China, 361005
2. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD, 20892
3. Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430074
4. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA 02138
5. Division of Hematology/Oncology, Department of Medicine and Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, SLB-05, Boston, MA 02215
6. Caliper Life Sciences, Inc., 68 Elm Street, Hopkinton, MA 01748
* Lei Zhu and Ning Guo contributed equally.


Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/64Cu dual-labeled cyclic RGD peptide.

Methods: The integrin αvβ3 binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data.

Results: The dual-labeled probe 64Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026).

Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.

Keywords: dual modality imaging, dynamic imaging, kinetic modeling, Singular value decomposition (SVD), integrin αvβ3, RGD peptide.

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How to cite this article:
Zhu L, Guo N, Li Q, Ma Y, Jacboson O, Lee S, Choi HS, Mansfield JR, Niu G, Chen X. Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe. Theranostics 2012; 2(8):746-756. doi:10.7150/thno.4762. Available from