Journal: Bioconjugate Chemistry

Abbreviation

Bioconjug. Chem.

Publisher

American Chemical Society

Journal Volumes

ISSN

1043-1802
1520-4812

Description

Filters

Reset filters

Search Results

Publications 1 - 10 of 57
  • Selection of Streptavidin Binders from a DNA-Encoded Chemical Library
    Item type: Journal Article
    Dumelin, Christoph E.; Scheuermann, Jörg; Melkko, Samu; et al. (2006)
    Bioconjugate Chemistry
  • Site-specific and stoichiometric conjugation of cationic porphyrins to antiangiogenic monoclonal antibodies
    Item type: Journal Article
    Alonso, Cristina M. A.; Palumbo, Alessandro; Bullous, Aaron J.; et al. (2010)
    Bioconjugate Chemistry
  • Comparative Studies of Three Pairs of α- and γ-Conjugated Folic Acid Derivatives Labeled with Fluorine-18
    Item type: Journal Article
    Boss, Silvan D.; Betzel, Thomas; Müller, Cristina; et al. (2016)
    Bioconjugate Chemistry
    The folate receptor (FR) is upregulated in various epithelial cancer types (FR α-isoform), while healthy tissues show only restricted expression. FR-targeted imaging using folate radiopharmaceuticals is therefore a promising approach for the detection of FR-positive cancer tissue. Almost all folate-based radiopharmaceuticals have been prepared by conjugation at the γ-carboxylic functionality of the glutamate moiety of folic acid. In this work, three pairs of fluorinated α- and γ-conjugated folate derivatives were synthesized and their in vitro and in vivo properties compared. The syntheses of all six regioisomers were obtained in good chemical yields using a multistep synthetic approach including the highly selective Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radiosyntheses of the α- and γ-conjugated 18F-labeled folate derivatives were accomplished in moderate to good radiochemical yields, high radiochemical purities (>95%), and specific activities ranging from 25 to 196 GBq/μmol. In vitro, all folate derivatives showed high binding affinity to the FR-α (IC50 = 1.4–2.2 nM). In vivo PET imaging and biodistribution studies in FR-positive KB tumor-bearing mice demonstrated similar FR-specific tumor uptake for both regioisomers of each pair of compounds. However, FR-unspecific liver uptake was significantly lower for the α-regioisomers compared to the corresponding γ-regioisomers. In contrast, kidney uptake was up to 50% lower for the γ-regioisomers than for the α-regioisomers. These results show that the site of conjugation in the glutamyl moiety of folic acid has a significant impact on the in vivo behavior of 18F-based radiofolates, but not on their in vitro FR-binding affinity. These findings may potentially stimulate new directions for the design of novel 18F-labeled folate-based radiotracers.
  • Uptake and metabolism of a dual fluorochrome tat-nanoparticle in HeLa cells
    Item type: Journal Article
    Koch, A.M.; Reynolds, F.; Kircher, M.F.; et al. (2003)
    Bioconjugate Chemistry
  • N-Linked Glycosylation of Antibody Fragments in Escherichia coli
    Item type: Journal Article
    Lizak, Christian; Fan, Yao-Yun; Weber, Thomas Christian; et al. (2011)
    Bioconjugate Chemistry
  • Revival of Bioengineered Proteins as Carriers for Nucleic Acids
    Item type: Other Journal Item
    Scherer, David; Burger, Michael; Leroux, Jean-Christophe (2024)
    Bioconjugate Chemistry
  • Michael-type addition as a tool for surface functionalization
    Item type: Journal Article
    Heggli, Martin; Tirelli, Nicola; Zisch, Andreas; et al. (2003)
    Bioconjugate Chemistry
  • Fluorine-18 Click Radiosynthesis and Preclinical Evaluation of a New 18F-Labeled Folic Acid Derivative
    Item type: Journal Article
    Ross, Tobias L.; Honer, Michael; Lam, Phoebe Y.H.; et al. (2008)
    Bioconjugate Chemistry
    The folate receptor (FR) is highly expressed on most epithelial cancer cells, while normal cells show only restricted expression of FR. As a result, the FR is an ideal target for receptor-based molecular imaging and therapy of cancer and has become a promising target in oncology. To date, several folate-based chemotherapeutics and imaging probes such as radiopharmaceuticals for single photon emission computed tomography (SPECT) have been developed. However, an 18F-labeled folic acid derivative suitable for positron emission tomography (PET) imaging that can be routinely applied is still lacking. In this study, a new fluorinated and radiofluorinated folic acid derivative, 18/19F-click folate, was synthesized using click chemistry. In a convenient and very efficient two-step radiosynthesis, the isolated 18F-click folate was obtained in good radiochemical yields of 25−35% with a specific activity of 160 ± 70 GBq/μmol after ≤90 min synthesis time. The new compound was pharmacologically evaluated in vitro and in vivo. The affinity of the non-radioactive 19F-click folate to the FR was determined in displacement studies with FR expressing KB tumor cells using 3H-folic acid. In these in vitro binding studies, a nanomolar affinity with a Ki of 9.76 ± 3.13 nM was found for 19F-click folate. The 18F-labeled click folate derivative was then applied for in vivo PET studies and ex vivo biodistribution experiments using nude mice bearing KB tumor xenografts. The post mortem dissection experiments showed a high specific uptake of 18F-click folate derivative in FR-expressing tissues. Uptake in KB tumor xenografts and kidneys (FR-positive tissue) amounted to 3.13%ID/g (94% specific blockade) and 16.53%ID/g (75% specific blockade), respectively. PET imaging using 18F-click folate permitted a visualization of KB tumors, and blockade studies confirmed the specific accumulation of the radiotracer in vivo. However, strong hepatobiliary excretion of the new tracer led to elevated accumulation of radioactivity in the abdominal region. In conclusion, the click chemistry approach is convenient to accomplish and provided high radiochemical yields of 18F-click folate. The new tracer showed good in vitro but limited in vivo properties. Ultimately, the 18F-click folate emphasizes the potential of 18F-labeled folates for receptor-based tumor PET imaging.
  • Synthesis, 18F-Labelling, and in Vitro and in Vivo Studies of Bombesin Peptides Modified with Silicon-Based Building Blocks
    Item type: Journal Article
    Höhne, Aileen; Mu, Linjing; Honer, Michael; et al. (2008)
    Bioconjugate Chemistry
  • Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody–Drug Conjugates
    Item type: Journal Article
    Dal Corso, Alberto; Cazzamalli, Samuele; Gébleux, Rémy; et al. (2017)
    Bioconjugate Chemistry
Publications 1 - 10 of 57