²¹²Pb in targeted radionuclide therapy: a review

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 ²¹²Bi, ²¹²Pb has seen increasing therapeutic use on account of its favourable chemistry, half-life, and decay properties. This review comprehensively discusses the clinical development of ²¹²Pb in recent years, particularly its production, chelation chemistry, and therapeutic adoption.

Improvements in generator technology and supply have overcome the historically limited availability of ²¹²Pb, enabling a surge of research in the field. Numerous bifunctional chelators have since been developed, which enable facile conjugation of ²¹²Pb to a plethora of tumour targeting carriers. Advancements in nuclear imaging techniques, and the use ²⁰³Pb as an imaging surrogate, have enabled accurate biodistribution and dosimetry information to inform preclinical studies. These factors have attracted considerable commercial interest in ²¹²Pb, culminating in the rapid translation of this radionuclide into the clinic, where it is being investigated in the treatment of a range of malignancies.

Radiotherapy with ²¹²Pb has shown enormous promise in preclinical and clinical studies. While challenges still remain before ²¹²Pb can be more widely adopted, remarkable progress has been made in addressing these. At present, the therapeutic potential of ²¹²Pb is only beginning to be realised.