Advances in Drug Design of Radiometal-Based Imaging Agents for Bone Disorders

Nuclear medicine bone imaging has been the optimum diagnosis for the detection of bone disorders because the lesion could be detectable before the appearance of symptomatic and radiographic changes. Over the past three decades, 99m Tc-MDP and 99m Tc-HMDP have been used as bone scintigraphic agents because of their superior biodistribution characteristics, although they are far from optimal from a chemical and pharmaceutical point of view. Recently, a more logical drug design has been proposed as a concept of bifunctional radiopharmaceuticals in which the carrier molecules (bisphosphonates) and radiometal chelating groups are separated within a molecule, specifically, 99m Tc-mononuclear complex-conjugated bisphosphonate. Some of the 99m Tc-mononuclear complex-conjugated bisphosphonate compounds showed superior biodistribution in preclinical studies. Moreover, the drug design concept could be applied to 68 Ga PET bone imaging agents. These studies would provide useful information for the development of radiometal-based imaging and therapeutic agents for bone disorders such as bone metastases.