Click Chemistry for 18F-Labeling of RGD Peptides and microPET Imaging of Tumor Integrin αvβ3 Expression

The cell adhesion molecule integrin αvβ3 plays a key role in tumor angiogenesis and metastasis. A series of 18F-labeled RGD peptides have been developed for PET of integrin expression based on primary amine reactive prosthetic groups. In this study, we report the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as a click reaction, to label RGD peptides with 18F by forming 1,2,3-triazoles. Nucleophilic fluorination of a toluenesulfonic alkyne provided 18F-alkyne in high yield (nondecay-corrected yield: 65.0 ± 1.9%, starting from the azeotropically dried 18F-fluoride), which was then reacted with an RGD azide (nondecay-corrected yield: 52.0 ± 8.3% within 45 min including HPLC purification). The 18F-labeled peptide was subjected to microPET studies in murine xenograft models. Murine microPET experiments showed good tumor uptake (2.1 ± 0.4%ID/g at 1 h postinjection (p.i.)) with rapid renal and hepatic clearance of 18F-fluoro-PEG-triazoles-RGD2 (18F-FPTA-RGD2) in a subcutaneous U87MG glioblastoma ...

[1]  W. Cai,et al.  18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of αvβ3 integrin expression , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  M. Glaser,et al.  "Click labeling" with 2-[18f]fluoroethylazide for positron emission tomography. , 2007, Bioconjugate chemistry.

[3]  L. Silengo,et al.  Quantification of the expression level of integrin receptor αvβ3 in cell lines and MR imaging with antibody‐coated iron oxide particles , 2006 .

[4]  J. Sutcliffe,et al.  Click for PET: rapid preparation of [18F]fluoropeptides using CuI catalyzed 1,3-dipolar cycloaddition , 2006 .

[5]  Horst Kessler,et al.  Positron Emission Tomography Using [18F]Galacto-RGD Identifies the Level of Integrin αvβ3 Expression in Man , 2006, Clinical Cancer Research.

[6]  Weibo Cai,et al.  A Thiol-Reactive 18F-Labeling Agent, N-[2-(4-18F-Fluorobenzamido)Ethyl]Maleimide, and Synthesis of RGD Peptide-Based Tracer for PET Imaging of αvβ3 Integrin Expression , 2006 .

[7]  Weibo Cai,et al.  Near-Infrared Fluorescence Imaging of Tumor Integrin αvβ3 Expression with Cy7-Labeled RGD Multimers , 2006, Molecular Imaging and Biology.

[8]  H. Hiemstra,et al.  CuI‐Catalyzed Alkyne—Azide “Click” Cycloadditions from a Mechanistic and Synthetic Perspective , 2006 .

[9]  K. Burgess,et al.  An iterative route to "decorated" ethylene glycol-based linkers. , 2006, Chemical communications.

[10]  G. Tron,et al.  Rapid synthesis of triazole-modified resveratrol analogues via click chemistry. , 2006, Journal of medicinal chemistry.

[11]  Yoav Eichen,et al.  Directed DNA metallization. , 2006, Journal of the American Chemical Society.

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

[13]  S. Gambhir,et al.  microPET Imaging of Glioma Integrin αvβ3 Expression Using 64Cu-Labeled Tetrameric RGD Peptide , 2005 .

[14]  Zoran Radić,et al.  In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors. , 2005, Journal of the American Chemical Society.

[15]  Longitudinal MicroPET Imaging of Brain Tumor Growth with F-18-labeled RGD Peptide , 2005, Molecular Imaging and Biology.

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

[17]  Horst Kessler,et al.  Two-step methodology for high-yield routine radiohalogenation of peptides: (18)F-labeled RGD and octreotide analogs. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  J. Bading,et al.  Micro-PET Imaging of αvβ3-Integrin Expression with 18F-Labeled Dimeric RGD Peptide , 2004 .

[19]  S. Simon,et al.  Ultrasonic Analysis of Peptide- and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αvβ3-Expressing Cells , 2004 .

[20]  M. Schwaiger,et al.  [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. , 2004, Bioconjugate chemistry.

[21]  C. Rüegg,et al.  Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis , 2003, Cellular and Molecular Life Sciences CMLS.

[22]  S. Kaul,et al.  Imaging Tumor Angiogenesis With Contrast Ultrasound and Microbubbles Targeted to (cid:1) v (cid:2) 3 , 2003 .

[23]  Luke G Green,et al.  A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. , 2002, Angewandte Chemie.

[24]  Morten Meldal,et al.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. , 2002, The Journal of organic chemistry.

[25]  R. Kalluri,et al.  Extracellular Matrix-derived Peptide Binds to αvβ3 Integrin and Inhibits Angiogenesis* , 2001, The Journal of Biological Chemistry.

[26]  D. Ribatti,et al.  αvβ3 integrin engagement modulates cell adhesion, proliferation, and protease secretion in human lymphoid tumor cells , 2001 .

[27]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[28]  G. Mizejewski,et al.  Role of integrins in cancer: survey of expression patterns. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[29]  David A. Cheresh,et al.  Detection of tumor angiogenesis in vivo by αvβ3-targeted magnetic resonance imaging , 1998, Nature Medicine.

[30]  K. Hamacher,et al.  A comparative study of N.C.A. fluorine-18 labeling of proteins via acylation and photochemical conjugation. , 1996, Nuclear medicine and biology.

[31]  J. Parsons,et al.  Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains , 1995, The Journal of cell biology.

[32]  K. Fujiwara,et al.  Focal adhesion proteins associated with apical stress fibers of human fibroblasts. , 1995, Cell motility and the cytoskeleton.

[33]  V. Garsky,et al.  Inhibition of osteoclastic bone resorption in vivo by echistatin, an "arginyl-glycyl-aspartyl" (RGD)-containing protein. , 1993, Endocrinology.

[34]  S. Albelda,et al.  Role of integrins and other cell adhesion molecules in tumor progression and metastasis. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[35]  D. Wilbur,et al.  Radiohalogenation of proteins: an overview of radionuclides, labeling methods, and reagents for conjugate labeling. , 1992, Bioconjugate chemistry.

[36]  M. Vaultier,et al.  Synthesis and Reactivity of Methyl γ-Azido Butyrates and Ethyl δ-Azido Valerates and of the Corresponding Acid Chlorides as Useful Reagents for Aminoalkylation. , 1987 .

[37]  C. Dence,et al.  Fluorine-18 labeling of proteins. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.