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.