IMoST - Proteoglycans PET imaging

SPECT/CT image with 99mTc-NTP 15-5 on rat bearing chondrosarcoma in the orthotopic paratibial location

We are synthesizing and studying new beta+ emitter complexes. Preliminary studies have resulted in the selection of copper-64 radiocomplexes pharmacomodulated with a quaternary ammonium function. Some have a biodistribution profile better than the ^99mTc-NTP 15-5 radiotracer (i.e. less hepatic fixation and increased specificity for aggrecans). These results have been patented in 2016. However, copper-64 has a too low availability (production/high cost) to become a relevant radiopharmaceutical.

The use of gallium-68 radionuclide would avoid the difficulties encountered with copper-64. Its production from a long-life and cost-effective generator makes it increasingly available in radiopharmacies. Moreover, its favorable branching ratio (89% beta+) and its short half-life (67.7 min) minimize the radiation dose to patients and personnel.

Many ligands functionalized with negatively charged pendant arms at physiological pH such as carboxylates, phosphonates, phosphinates have been developed for gallium-68 complexation but chelators with negatively charged pendant arms poorly interact with proteoglycans of articular cartilage. Our goal is to select a 68Ga-labeled bifunctional chelator with the best preclinical profile for cartilage functional PET imaging in humans.

Our work is organized around:

• organic syntheses of new ligands,
• gallium complexation studies,
• development of radiolabeling conditions,
• stability and biodistribution studies on small animals (mice, rats, rabbits),
• PET imaging assessments.