A review of advances in the last decade on targeted cancer therapy using 177Lu: focusing on 177Lu produced by the direct neutron activation route.

Lutetium-177 [T½ = 6.76 d; E_β (max) = 0.497 MeV; maximum tissue range ~2.5 mm; 208 keV γ-ray] is one of the most important theranostic radioisotope used for the management of various oncological and non-oncological disorders. The present review chronicles the advancement in the last decade in ¹⁷⁷Lu-radiopharmacy with a focus on ¹⁷⁷Lu produced via direct ¹⁷⁶Lu (n, γ) ¹⁷⁷Lu nuclear reaction in medium flux research reactors. The specific nuances of ¹⁷⁷Lu production by various routes are described and their pros and cons are discussed. Lutetium, is the last element in the lanthanide series. Its chemistry plays a vital role in the preparation of a wide variety of radiopharmaceuticals which demonstrate appreciable in vivo stability. Traditional bifunctional chelators (BFCs) that are used for ¹⁷⁷Lu-labeling are discussed and the upcoming ones are highlighted. Research efforts that resulted in the growth of various ¹⁷⁷Lu-based radiopharmaceuticals in preclinical and clinical settings are provided. This review also summarizes the results of clinical studies with potent ¹⁷⁷Lu-based radiopharmaceuticals that have been prepared using medium specific activity ¹⁷⁷Lu produced by direct neutron activation route in research reactors. Overall, the review amply demonstrates the practicality of the medium specific activity ¹⁷⁷Lu towards formulation of various clinically useful radiopharmaceuticals, especially for the benefit of millions of cancer patients in developing countries with limited reactor facilities.