Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to <sup>18</sup>F‐Glycopeptides as Effective Imaging Probes for Positron Emission Tomography

Maschauer, Simone; Einsiedel, Jürgen; Haubner, Roland; Hocke, Carsten; Ocker, Matthias; Hübner, Harald; Kuwert, Torsten; Gmeiner, Peter; Prante, Olaf

doi:10.1002/anie.200904137

Cited by 113 publications

(157 citation statements)

References 38 publications

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“…1). The resulting IC 50 values are comparable to the reference molecule c(RGDfV) and to reported IC 50 values of other RGD derivatives, such as galacto-RGD (IC 50 , 4.0 6 0.4 · 10 27 mol/L (14)) and others, studied in intact U87MG cells (17,18). The impact of the different chelators and radiometals on the integrinbinding affinity was thus modest, as has also been observed by other groups (19)(20)(21)(22).…”

Section: Discussionsupporting

confidence: 85%

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis

et al. 2011

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PET with 18 F-labeled arginine-glycine-aspartic acid (RGD) peptides can visualize and quantify a n b 3 integrin expression in patients, but radiolabeling is complex and image contrast is limited in some tumor types. The development of 68 Ga-RGD peptides would be of great utility given the convenience of 68 Ga production and radiolabeling, and 64 Cu-RGD peptides allow for delayed imaging with potentially improved tumor-tobackground ratios. Methods: We used the chelators DOTA,1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), and 4,11-bis(carboxymethyl)-1, 4,8,11-tetraazabicyclo[6.6.2] hexadecane (CB-TE2A) to radiolabel the cyclic pentapeptide c(RGDfK) with 68 Ga or 64 Cu. NODAGA-c(RGDfK) was labeled at room temperature with both radionuclides within 10 min. Incubation at 95°C for up to 30 min was used for the other conjugates. The affinity profile of the metallopeptides was evaluated by a cell-based receptor-binding assay. Small-animal PET studies and biodistribution studies were performed in nude mice bearing subcutaneous U87MG glioblastoma xenografts. Results: The conjugates were labeled with a radiochemical purity greater than 97% and specific activities of 15-20 GBq/mmol. The affinity profile was similar for all metallopeptides and comparable to the reference standard c(RGDfV). In the biodistribution studies, all compounds demonstrated a relatively similar tumor and normal organ uptake at 1 h after injection that was comparable to published data on 18 F-labeled RGD peptides. At 18 h after injection, however, 64 Cu-NODAGA-c(RGDfK) and 64 Cu-CB-TE2A-c(RGDfK) showed up to a 20-fold increase in tumor-to-organ ratios. PET studies demonstrated high-contrast images of the U87MG tumors at 18 h, confirming the biodistribution data. Conclusion: The ease of radiolabeling makes 68 Ga-NODAGA-c(RGDfK) an attractive alternative to 18 F-labeled RGD peptides. The high tumor-to-background ratios of 64 Cu-NODAGA-c(RGDfK) and 64 Cu-CB-TE2A-c(RGDfK) at 18 h warrant testing of 64 Cu-labeled RGD peptides in patients.

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Section: Discussionsupporting

confidence: 85%

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis

et al. 2011

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“…9,12,13,34,35,40 Strikingly, tumor uptake of triazole-stabilized [ 177 Lu]-NT VI and IX was increased up to 2-fold (approximately 2% injected dose (ID)/g) in comparison to that of the corresponding reference compounds [ 177 Lu]-NT I and VIII, respectively (each approximately 1% ID/g). These results suggest that the introduction of a 1,2,3-triazole moiety between the Arg 9 -Arg 8 residues of NT(8−13) may represent a general approach to improve the tumor targeting properties of the peptide.…”

Section: Bioconjugate Chemistrymentioning

confidence: 99%

1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting

et al. 2015

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Neurotensin (NT) is a regulatory peptide with nanomolar affinity toward NT receptors, which are overexpressed by different clinically relevant tumors. Its binding sequence, NT(8-13), represents a promising vector for the development of peptidic radiotracers for tumor imaging and therapy. The main drawback of the peptide is its short biological half-life due to rapid proteolysis in vivo. Herein, we present an innovative strategy for the stabilization of peptides using nonhydrolizable 1,4-disubstituted, 1,2,3-triazoles as amide bond surrogates. A "triazole scan" of the peptide sequence yielded novel NT(8-13) analogues with enhanced stability, retained receptor affinity, and improved tumor targeting properties in vivo. The synthesis of libraries of triazole-based peptidomimetics was achieved efficiently on solid support by a combination of Fmoc-peptide chemistry, diazo transfer reactions, and the Cu(I)-catalyzed alkyne azide cycloaddition (CuAAC) employing methods that are fully compatible with standard solid phase peptide synthesis (SPPS) chemistry. Thus, the amide-to-triazole substitution strategy may represent a general methodology for the metabolic stabilization of biologically active peptides.

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“…This probe exhibits good tumor-targeting efficacy and relatively good metabolic stability, as well as favorable in vivo pharmacokinetics. In 2009, Maschauer et al further extended the click chemistry for the synthesis of 18 F-glycopeptides for microPET imaging [52]. As mentioned for the preparation of 18 F-Galacto-RGD, the glycosylation of peptides is frequently used for the improvement of the pharmacokinetic and in vivo clearance properties of the probe.…”

Section: Click Chemistrymentioning

confidence: 99%

Recent Progress in Radiofluorination of Peptides for PET Molecular Imaging

Liu¹,

Shen²,

Chin³

et al. 2011

COS

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Because of its low positron energy, lack of side emission, and a moderate half-life, Fluorine-18 ( + , 0.635 MeV [97%], t1/2 = 109.8 min) has ideal physical properties for positron emission tomography (PET). With the increasing numbers of peptides that are potentially applicable for molecular imaging of diseases, novel and simple 18 F-labeling methods have been actively investigated and reported. In this review, a few well established and widely-used radiofluorination strategies are discussed. Novel approaches including click chemistry, one-step chelation labeling (i.e. Al 18 F-NOTA), and silicon-based 18 F labeling are described as well.

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Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to ¹⁸F‐Glycopeptides as Effective Imaging Probes for Positron Emission Tomography

Cited by 113 publications

References 38 publications

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis

1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting

Recent Progress in Radiofluorination of Peptides for PET Molecular Imaging

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Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to 18F‐Glycopeptides as Effective Imaging Probes for Positron Emission Tomography

Cited by 113 publications

References 38 publications

Novel 64Cu- and 68Ga-Labeled RGD Conjugates Show Improved PET Imaging of ανβ3 Integrin Expression and Facile Radiosynthesis

Novel 64Cu- and 68Ga-Labeled RGD Conjugates Show Improved PET Imaging of ανβ3 Integrin Expression and Facile Radiosynthesis

1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting

Recent Progress in Radiofluorination of Peptides for PET Molecular Imaging

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Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to ¹⁸F‐Glycopeptides as Effective Imaging Probes for Positron Emission Tomography

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis

Novel ⁶⁴Cu- and ⁶⁸Ga-Labeled RGD Conjugates Show Improved PET Imaging of α_νβ₃ Integrin Expression and Facile Radiosynthesis