68Ga-glucosamine analogs for PET imaging of cancer

Objectives ⁶⁸Ga-PET provides a cost-effective alternative to cyclotron produced PET agents, but is limited by the number of functional agents available. This study reports on development of ⁶⁸Ga-based glucosamine derivatives as new PET agents for cancer imaging.

Methods A small library of tetraazacyclododecane-glucosamine derivatives were prepared by coupling glucosamine to functional groups present on the chelators (i.e. methylene carboxy groups of DOTA). Reactions were performed in the presence of peptide coupling agents and purified by crystallization, extraction and subsequent precipitation. The compound was labeled with ⁶⁸Ga in acetate buffer and heated at 95^oC for 10-20 min. Radiochemical yield and purity were assessed. In vitro bioactivity was evaluated by cellular uptake studies and hexokinase (Hx) assay. MicroPET images were obtained using breast and colon tumor bearing models.

Results Multiple tetraazacyclododecane-glucosamine derivatives were synthesized with 50-60% yield, and structures were confirmed by NMR and mass spectrometry. Radiochemical yield was dependent on conjugation scheme, and was >95% for lead compounds. Cellular uptake studies showed increased accumulation in cancer cells as a function of time. The rates of phosphorylation by Hx were comparable for lead compounds, FDG and free glucosamine. Tumor localization was observed in animal models using micro PET.

Conclusions An efficient synthesis strategy was developed for ⁶⁸Ga-glucosamine conjugates. Preliminary studies show promise that ⁶⁸Ga-labeled glucosamine derivatives may be a broad-use, low-cost alternative for PET imaging of tumors.