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

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.

[1]  Lixin Lang,et al.  Quantitative Analysis and Parametric Imaging of 18F-Labeled Monomeric and Dimeric RGD Peptides Using Compartment Model , 2012, Molecular Imaging and Biology.

[2]  Samuel Achilefu,et al.  Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph node imaging , 2011, Biomedical optics express.

[3]  J. Tonn,et al.  Molecular imaging of gliomas with PET: opportunities and limitations. , 2011, Neuro-oncology.

[4]  Hak Soo Choi,et al.  Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. , 2011, Angewandte Chemie.

[5]  M. Rosenblum,et al.  Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment. , 2011, Molecular pharmaceutics.

[6]  N. Neamati,et al.  Integrin Targeted Therapeutics , 2011, Theranostics.

[7]  Young T. Hong,et al.  Parametric Mapping of [18F]Fluoromisonidazole Positron Emission Tomography using Basis Functions , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  F. Kiessling,et al.  Integrin Targeting for Tumor Optical Imaging , 2011, Theranostics.

[9]  F. Kiessling,et al.  Why Integrin as a Primary Target for Imaging and Therapy , 2011, Theranostics.

[10]  N. Neamati,et al.  18F-FPPRGD2 and 18F-FDG PET of Response to Abraxane Therapy , 2011, The Journal of Nuclear Medicine.

[11]  Alexander L. Vahrmeijer,et al.  Optical Image-guided Surgery—Where Do We Stand? , 2010, Molecular Imaging and Biology.

[12]  M. Hutchinson,et al.  Use of Imaging Techniques to Guide Catheter Ablation Procedures , 2010, Current cardiology reports.

[13]  G. Niu,et al.  Preclinical molecular imaging of tumor angiogenesis. , 2010, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[14]  Andrea Carter.  Integrins as target: first phase III trial launches, but questions remain. , 2010, Journal of the National Cancer Institute.

[15]  Ralph P. Mason,et al.  Dynamic Near-Infrared Optical Imaging of 2-Deoxyglucose Uptake by Intracranial Glioma of Athymic Mice , 2009, PloS one.

[16]  H. Kessler,et al.  Ligands for Mapping a v 3 -Integrin Expression in Vivo , 2009 .

[17]  K. Shoghi,et al.  Quantitative small animal PET. , 2009, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[18]  Sung-Cheng Huang,et al.  Derivation of a Compartmental Model for Quantifying 64Cu-DOTA-RGD Kinetics in Tumor-Bearing Mice , 2009, Journal of Nuclear Medicine.

[19]  Chenjie Xu,et al.  PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles , 2008, Journal of Nuclear Medicine.

[20]  Weibo Cai,et al.  Multimodality Molecular Imaging of Tumor Angiogenesis , 2008, Journal of Nuclear Medicine.

[21]  Sanjiv S. Gambhir,et al.  Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature , 2007, Journal of Nuclear Medicine.

[22]  E. Hillman,et al.  All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast. , 2007, Nature photonics.

[23]  W. Cai,et al.  64Cu-Labeled Tetrameric and Octameric RGD Peptides for Small-Animal PET of Tumor αvβ3 Integrin Expression , 2007, Journal of Nuclear Medicine.

[24]  Sanjiv S. Gambhir,et al.  How molecular imaging is speeding up antiangiogenic drug development , 2006, Molecular Cancer Therapeutics.

[25]  M. Schwaiger,et al.  Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  Eva M. Sevick-Muraca,et al.  Quantifying molecular specificity of αvβ3 integrin-targeted optical contrast agents with dynamic optical imaging , 2005 .

[27]  Ralph Weissleder,et al.  Molecular optical imaging: Applications leading to the development of present day therapeutics , 2005, NeuroRX.

[28]  R. Moats,et al.  In vivo Near-Infrared Fluorescence Imaging of Integrin αvβ3 in Brain Tumor Xenografts , 2004, Cancer Research.

[29]  A B Thompson,et al.  Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies. , 2004, Journal of biomedical optics.

[30]  Jean Logan,et al.  A review of graphical methods for tracer studies and strategies to reduce bias. , 2003, Nuclear medicine and biology.

[31]  Y. Hoshi.  Functional near-infrared optical imaging: utility and limitations in human brain mapping. , 2003, Psychophysiology.

[32]  Sibylle Ziegler,et al.  Noninvasive Imaging of αvβ3 Integrin Expression Using 18F-labeled RGD-containing Glycopeptide and Positron Emission Tomography , 2001 .

[33]  P. Ell,et al.  Clinical role of positron emission tomography in oncology. , 2001, The Lancet. Oncology.

[34]  M. Phelps,et al.  PET: the merging of biology and imaging into molecular imaging. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[35]  D Delbeke,et al.  Oncological applications of FDG PET imaging: brain tumors, colorectal cancer, lymphoma and melanoma. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  N. Volkow,et al.  Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[37]  David J. Schlyer,et al.  Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [N-11C-Methyl]-(−)-Cocaine PET Studies in Human Subjects , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[38]  Charles L. Lawson,et al.  Solving least squares problems , 1976, Classics in applied mathematics.

[39]  K. Miller.  Least Squares Methods for Ill-Posed Problems with a Prescribed Bound , 1970 .

[40]  S. Gambhir,et al.  Quantitative PET Imaging of Tumor Integrin αvβ3 Expression with 18F-FRGD2 , 2006 .

[41]  R. Weissleder,et al.  Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging , 2002, European Radiology.