Ga-68-Labeled bismacrocyclic methylene phosphonate as potential bone seeking PET radiopharmaceutical

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. Ga-68-based generator and radiotracers render independence from the on-site cyclotron. We report the development of Ga-68-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of (68)GaDO3P-AME-DO3P was carried out in 95% purity. The radiotracer displayed high stability and low binding affinity (< 3%) to blood serum. High in vitro binding affinity were observed for synthetic hydroxyapatite, SAOS-2, osteoclast and osteoblast cells. In vivo pharmacokinetics revealed fast washout with biphasic release pattern. The deposition of radiotracer in osseous tissues was high (Bone/Muscle ratio:18), as studied from the biodistribution studies. In vivo PET/CT and biodistribution analyses revealed the ability of Ga-68-DO3P-AME-DO3P to target and accumulate in bone, thus displaying its potential as a PET bone imaging agent.