Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Oxime Coupling of Active Site Inhibited Factor Seven with a Nonvolatile, Water-Soluble Fluorine-18 Labeled Aldehyde

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Affinity-Guided Conjugation to Antibodies for Use in Positron Emission Tomography

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Effect of liraglutide on expression of inflammatory genes in type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Ceramides and phospholipids are downregulated with liraglutide treatment: results from the LiraFlame randomized controlled trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Effect of Liraglutide on Vascular Inflammation Evaluated by [64Cu]DOTATATE

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

A nonvolatile fluorine-18 aldehyde prosthetic group was developed from [18F]SFB, and used for site-specific labeling of active site inhibited factor VII (FVIIai). FVIIai has a high affinity for tissue factor (TF), a transmembrane protein involved in angiogenesis, proliferation, cell migration, and survival of cancer cells. A hydroxylamine N-glycan modified FVIIai (FVIIai-ONH2) was used for oxime coupling with the aldehyde [18F]2 under mild and optimized conditions in an isolated RCY of 4.7 ± 0.9%, and a synthesis time of 267 ± 5 min (from EOB). Retained binding and specificity of the resulting [18F]FVIIai to TF was shown in vitro. TF-expression imaging capability was evaluated by in vivo PET/CT imaging in a pancreatic human xenograft cancer mouse model. The conjugate showed exceptional stability in plasma (>95% at 4 h) and a binding fraction of 90%. In vivo PET/CT imaging showed a mean tumor uptake of 3.8 ± 0.2% ID/g at 4 h post-injection, a comparable uptake in liver and kidneys, and low uptake in normal tissues. In conclusion, FVIIai was labeled with fluorine-18 at the N-glycan chain without affecting TF binding. In vitro specificity and a good in vivo imaging contrast at 4 h postinjection was demonstrated.

Original languageEnglish
JournalBioconjugate Chemistry
Volume30
Issue number3
Pages (from-to)775-784
ISSN1043-1802
DOIs
Publication statusPublished - 20 Mar 2019

ID: 56694945