Abstract
BACKGROUND: The selective delivery of α-emitting radionuclides is emerging as a highly effective form of cancer therapy. With a short range and high cytotoxicity, α-particles can selectively kill cancerous cells whilst minimising harm to surrounding healthy tissue. As the parent of the α-emitter (212)Bi, (212)Pb has seen increasing therapeutic use on account of its favourable chemistry, half-life, and decay properties. This review comprehensively discusses the clinical development of (212)Pb in recent years, particularly its production, chelation chemistry, and therapeutic adoption. MAIN BODY: Improvements in generator technology and supply have overcome the historically limited availability of (212)Pb, enabling a surge of research in the field. Numerous bifunctional chelators have since been developed, which enable facile conjugation of (212)Pb to a plethora of tumour targeting carriers. Advancements in nuclear imaging techniques, and the use (203)Pb as an imaging surrogate, have enabled accurate biodistribution and dosimetry information to inform preclinical studies. These factors have attracted considerable commercial interest in (212)Pb, culminating in the rapid translation of this radionuclide into the clinic, where it is being investigated in the treatment of a range of malignancies. CONCLUSION: Radiotherapy with (212)Pb has shown enormous promise in preclinical and clinical studies. While challenges still remain before (212)Pb can be more widely adopted, remarkable progress has been made in addressing these. At present, the therapeutic potential of (212)Pb is only beginning to be realised.