Development of Potential 177Lu Radiopharmaceuticals: Design, Radiolabelling and Nonclinical Evaluation

Lutetium-177 (177Lu) is currently the most important therapeutic radionuclide and it will continue to be the key role player in the nuclear medicine field in the developed and developing world. Radionuclide decay characteristics of 177Lu have specific advantages for this purpose. Eβ(max) = 497 keV offers LET with 1-2 mm effective radiation radius supporting targeted therapy at cellular level and gamma radiation component of Eg = 113 keV (6.4%) and 208 keV(11%), allows organ dosimetry. 177Lu decays to stable hafnium making waste management and patient safety easy. Its half-life of 6.65 days permits logistic of production and supply of radioisotope and finished product. The convenient half-life and lutetium chemistry supports using varying types of pharmacological carrier molecules and design radiopharmaceutical with desired pharmacokinetics to achieve high target to non-target organ ratios. Currently there are over 70 radiopharmaceuticals for therapy in clinical trials and about 40% of them are based on 177Lu alone. The mainstream includes radiopharmaceuticals for neuroendocrine tumors and prostate cancer, and this list is expected to grow fast for other indications, thanks to the identification of new biological targets and targeting vectors such as peptides, peptidomimetics, monoclonal antibodies and their engineered fragments, aptamers, targeting nanoparticles etc. This Coordinated Research Project (CRP) will identify potential carrier molecules that target some of the major cancers for labelling with 177Lu using bifunctional agents and carry out preclinical evaluation towards the development of radiopharmaceuticals for targeted therapy.?