Direct labelling of peptides with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG)

doi:10.1016/j.bmcl.2009.07.108

Bioorganic & Medicinal Chemistry Letters

Volume 19, Issue 18, 15 September 2009, Pages 5426-5428

https://doi.org/10.1016/j.bmcl.2009.07.108 Get rights and content

Abstract

The study describes the use of [¹⁸F]FDG as ¹⁸F building block for the direct labelling of various aminooxy-functionalised peptides via chemoselective oxime formation.

Graphical abstract

References and notes (11)

H.-J. Wester et al.
Ernst Schering Res. Found. Workshop
(2007)
J. Marik et al.
Tetrahedron Lett.
(2006)
M. Glaser et al.
Bioconjug. Chem.
(2007)
Z.B. Li et al.
Bioconjug. Chem.
(2007)
T. Ramenda et al.
Lett. Drug Des. Discovery
(2007)
M. Leisner et al.
J. Label. Compd. Radiopharm.
(1999)
R. Haubner et al.
Cancer Res.
(2001)
M. Schottelius et al.
Bioconjug. Chem.
(2002)
M. Schottelius et al.
J. Med. Chem.
(2005)
M. Schottelius et al.
Bioconjug. Chem.
(2005)
H.-J. Wester et al.
Cancer Biother. Radiopharm.
(2004)

There are more references available in the full text version of this article.

Cited by (42)

Efficient cartridge purification for producing high molar activity 18F-glycoconjugates via oxime formation
2018, Nuclear Medicine and Biology
Citation Excerpt :
The peaks belong to the acyclic E- and Z-isomers, and the cyclic pyranose isomer. Previous studies have also reported the formation of different isomers with hexose conjugates [14,17,18,39]. TOF-ESI-MS [M + H]+ m/z calcd.
¹⁸F-fluoroglycosylation via oxime formation is a chemoselective and mild radiolabeling method for sensitive molecules. Glycosylation can also improve the bioavailability, in vivo kinetics, and stability of the compound in blood, as well as accelerate clearance of biomolecules. A typical synthesis procedure for ¹⁸F-fluoroglycosylation with [¹⁸F]FDG (2-deoxy-2-[¹⁸F]fluoro-d-glucose) and [¹⁸F]FDR (5-deoxy-5-[¹⁸F]fluoro-d-ribose) involves two HPLC (high performance liquid chromatography) purifications: one after ¹⁸F-fluorination of the carbohydrate to remove its labeling precursor, and a second one after the oxime formation step to remove the aminooxy precursor. The two HPLC purifications can be time consuming and complicate the adaptation of the synthetic strategy in nuclear medicine applications and automated synthesis. We have developed a procedure in which SPE (solid phase extraction) and resin purification methods replace both of the needed HPLC purification steps.
We used [¹⁸F]FDR and [¹⁸F]FDG as prosthetic groups to radiolabel two aminooxy-modified model molecules, a tetrazine and a PSMA (prostate specific membrane antigen) inhibitor. After fluorination, the excess carbohydrate precursor was removed by derivatizing it with 4,4′-dimethoxytrityl chloride (DMT-Cl). The DMT moiety increases the hydrophobicity of the unreacted precursor making the separation from the fluorinated precursor possible with simple C18 Sep-Pak cartridge. For removal of the aminooxy precursor, we used a commercially available aldehyde resin (AminoLink, Thermo Fisher Scientific). C18 Sep-Pak SPE cartridge was used to separate [¹⁸F]FDR and [¹⁸F]FDG from the ¹⁸F-fluoroglycoconjugate end product.
[¹⁸F]FDR and [¹⁸F]FDG were efficiently purified from their precursors, free fluorine-18, and other impurities. The aldehyde resin quantitatively removed the unreacted aminooxy precursors after the oxime formation. The fluorine-18 labeled oxime end products were obtained with high radiochemical purity (>99%) and molar activity (>600 GBq μmol⁻¹).
We have developed an efficient cartridge purification method for producing high molar activity ¹⁸F-glycoconjugates synthesized via oxime formation.
Molecular imaging probes derived from natural peptides
2016, Natural Product Reports
Covering: up to the end of 2015.
Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available.
Caged [18F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography
2016, Bioconjugate Chemistry
Solid tumors are hypoxic with altered metabolism, resulting in secretion of acids into the extracellular matrix and lower relative pH, a feature associated with local invasion and metastasis. Therapeutic and diagnostic agents responsive to this microenvironment may improve tumor-specific delivery. Therefore, we pursued a general strategy whereby caged small-molecule drugs or imaging agents liberate their parent compounds in regions of low interstitial pH. In this manuscript, we present a new acid-labile prodrug method based on the glycosylamine linkage, and its application to a class of positron emission tomography (PET) imaging tracers, termed [¹⁸F]FDG amines. [¹⁸F]FDG amines operate via a proposed two-step mechanism, in which an acid-labile precursor decomposes to form the common radiotracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose, which is subsequently accumulated by glucose avid cells. The rate of decomposition of [¹⁸F]FDG amines is tunable in a systematic fashion, tracking the pK_a of the parent amine. In vivo, a 4-phenylbenzylamine [¹⁸F]FDG amine congener showed greater relative accumulation in tumors over benign tissue, which could be attenuated upon tumor alkalinization using previously validated models, including sodium bicarbonate treatment, or overexpression of carbonic anhydrase. This new class of PET tracer represents a viable approach for imaging acidic interstitial pH with potential for clinical translation.
Rerouting the metabolic pathway of 18F-labeled peptides: The influence of prosthetic groups
2015, Bioconjugate Chemistry
Current translational cancer research is directed to the development of high affinity peptide ligands for targeting neuropeptide receptors overexpressed in different types of cancer. Besides their desired high binding affinity to the receptor, the suitability of radiolabeled peptides as targeting vectors for molecular imaging and therapy depends on additional aspects such as high tumor-to-background ratio, favorable clearance pattern from nontarget tissue, and sufficient metabolic stability in vivo. This study reports how a switch from the prosthetic group, N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB), to 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) effects the metabolic pathway of an ¹⁸F-labeled bombesin derivative, QWAV-Sar-H-FA01010-Tle-NH₂. ¹⁸F-Labeled bombesin derivatives represent potent peptide ligands for selective targeting of gastrin-releasing peptide (GRP) receptor-expressing prostate cancer. Radiosynthesis of ¹⁸F-labeled bombesin analogues [¹⁸F]FBz-Ava-BBN2 and [¹⁸F]FDG-AOAc-BBN2 was achieved in good radiochemical yields of ∼50% at a specific activity exceeding 40 GBq/μmol. Both nonradioactive compounds FBz-Ava-BBN2 and FDG-AOAc-BBN2 inhibited binding of [¹²⁵I]Tyr⁴-bombesin(1–14) in PC3 cells with IC₅₀ values of 9 and 16 nM, respectively, indicating high inhibitory potency. Influence of each prosthetic group was further investigated in PC3 mouse xenografts using dynamic small animal PET imaging. In comparison to [¹⁸F]FBz-Ava-BBN2, total tumor uptake levels were doubled after injection of [¹⁸F]FDG-AOAc-BBN2 while renal elimination was increased. Blood clearance and in vivo metabolic stability were similar for both compounds. The switch from [¹⁸F]SFB to [¹⁸F]FDG as the prosthetic group led to a significant reduction in lipophilicity which resulted in more favorable renal clearance and increased tumor uptake. The presented single step radiolabeling-glycosylation approach represents an innovative strategy for site-directed peptide labeling with the short-lived positron emitter ¹⁸F while providing a favorable pharmacokinetic profile of ¹⁸F-labeled peptides.
A one-pot enzymatic approach to the O-fluoroglucoside of N-methylanthranilate
2013, Bioorganic and Medicinal Chemistry
In connection with prospective ¹⁸F-PET imaging studies, the potential for enzymatic synthesis of fluorine-labelled glycosides of small molecules was investigated. Approaches to the enzymatic synthesis of anomeric phosphates of d-gluco-configured fluorosugars proved ineffective. In contrast, starting in the d-galacto series and relying on the consecutive action of Escherichia coli galactokinase (GalK), galactose-1-phosphate uridylyltransferase (GalPUT), uridine-5′-diphosphogalactose 4-epimerase (GalE) and oat root glucosyltransferase (SAD10), a quick and effective synthesis of 6-deoxy-6-fluoro-d-glucosyl N-methylanthranilate ester was achieved.
Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of trans-Cyclooctene-Functionalized Molecular Spherical Nucleic Acids
2023, ACS Omega

View all citing articles on Scopus

^☆: See note †.

View full text

Article preview

Bioorganic & Medicinal Chemistry Letters

Abstract

Graphical abstract

References and notes (11)

Ernst Schering Res. Found. Workshop

Tetrahedron Lett.

Bioconjug. Chem.

Bioconjug. Chem.

Lett. Drug Des. Discovery

J. Label. Compd. Radiopharm.

Cancer Res.

Bioconjug. Chem.

J. Med. Chem.

Bioconjug. Chem.

Cancer Biother. Radiopharm.

Cited by (42)

Efficient cartridge purification for producing high molar activity <sup>18</sup>F-glycoconjugates via oxime formation

Molecular imaging probes derived from natural peptides

Caged [<sup>18</sup>F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography

Rerouting the metabolic pathway of <sup>18</sup>F-labeled peptides: The influence of prosthetic groups

A one-pot enzymatic approach to the O-fluoroglucoside of N-methylanthranilate

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of trans-Cyclooctene-Functionalized Molecular Spherical Nucleic Acids

Direct labelling of peptides with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG)☆

Abstract

Graphical abstract

Ernst Schering Res. Found. Workshop

Tetrahedron Lett.

Bioconjug. Chem.

Bioconjug. Chem.

Lett. Drug Des. Discovery

J. Label. Compd. Radiopharm.

Cancer Res.

Bioconjug. Chem.

J. Med. Chem.

Bioconjug. Chem.

Cancer Biother. Radiopharm.

Direct labelling of peptides with 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]FDG)☆