Theranostics of Bone Metastases: The Role and Prospects of Bisphosphonate Radiopharmaceuticals

Bone metastasis is among the most common complications of advanced malignant tu-mors and severely affects prognosis in patients. Nuclear medicine, particularly bone-targeted radiopharmaceuticals, plays a unique and pivotal role in the diagnosis and treatment of bone metastases. This review systematically outlines the evolutionary trajec-tory of bone-targeted radiopharmaceuticals. It revisits functional bone imaging agents based on Single Photon Emission Computed Tomography (SPECT) and Positron Emis-sion Tomography (PET), as well as recently developed therapeutic radiopharmaceuticals for bone metastases. Building on this foundation, this article focuses on the advanced paradigm of “theranostics” in nuclear medicine, encompassing strategies for theranostic radionuclide pairing and the development of single-radionuclide theranostic agents, aiming to achieve individualized and precise dosimetry. Moreover, this review empha-sizes bone-targeting molecular scaffolds, such as bisphosphonates, and highlights their potential and direction for optimization through rational drug design, with the goal of developing a new generation of highly effective and low-toxicity theranostic platforms. This work aims to provide systematic insights for enhancing the precise management of bone metastases.