Development of a new, miniaturized 18F marking method for proteins and peptides with 18 F-FDG as a building block

01 January 2010 → 31 December 2015
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Biomarker discovery and evaluation
    • Drug discovery and development
    • Medicinal products
    • Pharmaceutics
    • Pharmacognosy and phytochemistry
    • Pharmacology
    • Pharmacotherapy
    • Toxicology and toxinology
    • Other pharmaceutical sciences
18F marking method
Project description

In the current proposal, we like would like to explore : (1) the possibility of using 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) as a building block for the radiosynthesis of 18F-labeled compounds. Being the most important radiotracer for PET imaging in nuclear medicine, [18F]FDG is available in almost every PET center. The [18F]FDG based building blocks will then be evaluated for the labeling of proteins, using in house developped Fab and Scfragments, derived from the 14C5 monoclonal antibody, which targets the αvβ5 integrine8,9. By using this in house model the in vitro binding characteristics (Ki, immunoreactivity) and in vivo properties of the newly developed [18F]FDG based prosthetic groups can be compared to the standard labeling procedures with 123I and 111In. (2) In a second step we would like to miniaturize the synthesis strategy using μicrofluids based PET chemistry. (3) The developed synthesis strategy will be applied to two new biomarker targets, respectively the insulin-like growth-factor 1 receptor (IGF1R)16 and fascin-115. The insulin-like growth factor pathway (IGF1/IG1-receptor) plays a major role in cancer cell proliferation, survival and resistance to anti-cancer therapies in many human malignancies, including breast cancer. Thus, in-vivo visualization of IGF-1R in a non-invasive manner using 18F-labelled des-IGF1 may allow for prediction of chemosensitivity and selection of patients that might benefit from novel IGF-1R blocking strategies. Fascin-1 is an actin-binding protein that promotes cell proliferation, adhesion and motility, Higher expression of fascin-1 has been shown to correlate with tumor grades and stages in a variety of human malignancies. In vivo visualization of fascin-1 expression by means of 18F-labelled fascin-1 targeting Fab fragments may non-invasively predict clinico-pathological parameters.