Safely developing an 18F-Labeling Maltose Dendrimer Radiotracer for Positron Emission Tomography (PET) Imaging of Heparanase

Yinglan Pu | University of AlbertaEnoch ABC Ballroom

Background: Heparanase, the only mammalian enzyme capable of degrading heparan sulfate (HS), plays a crucial role in various cellular processes including angiogenesis, inflammation, and cancer cell metastasis. Its overexpression in cancer cells makes it an attractive target for anti-cancer therapies. However, the development of heparanase-targeting radiotracers for positron emission tomography (PET) diagnostic imaging or for cancer treatments has been limited. In this study, we utilized a dendrimer HS glycomimetic heparanase inhibitor as a precursor to develop a Fluorine-18 labeled PET imaging agent.

Methods and Results: Our radiotracer was crafted by replacing one arm of the dendrimer with a fragment containing a silicon-fluoride acceptor (SiFA) moiety. Assessment of the radiotracer’s binding to heparanase was conduct using a colorimetric affinity assay based on Ferro’s method, yielding a reasonable 200 nM IC50. Fluorine-18 was effectively introduced to the SiFA group using an improved isotopic exchange reaction, resuting in a radiochemical yield of 93 % ± 0.5%. This is followed by a brief 15-minute chemistry step to form the radiotracer. Subsequent HPLC purification and solvent removal were performed, yielding a sample ready for animal injection.

Conclusion: We have developed a novel F-18 labeled heparanase inhibitor for oncological PET imaging. Future steps involve in vitro and in vivo analysis in various breast cancer models. The precautions for radiation protection have been outlined, ensuring safety during the labeling process.

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