Emergence and present status of Lu-177 in targeted radiotherapy: the Indian scenario

Abstract

¹⁷⁷Lu is presently considered to be a potential radionuclide for the development of agents for radionuclide therapy owing to its favorable nuclear decay characteristics [T_1/2 = 6.65 d, E_β(max) = 0.497 MeV, E_γ = 113 KeV (6.4%) and 208 KeV (11%)]. While the long half-life of this promising radioisotope offers distinct logistic advantage, particularly, in countries having limited reactor facilities, the feasibility of its large-scale production with adequate specific activity and excellent radionuclidic purity in medium flux research reactors constitute yet another desirable feature. Extensive studies have been carried out to optimize the production of this isotope, with high specific activity and radionuclidic purity by the (n,γ) route using the highest available flux and the optimum irradiation time. The gradual evolution of clin ical grade ¹⁷⁷LuCl₃ as a new radiochemical, ready for commercial deployment by Radiopharmaceuticals Division, Bhabha Atomic Research Centre, to nuclear medicine centers all over India was accomplished in 2010 in a stepwise manner with the commencement of the production of high specific activity ¹⁷⁷Lu from enriched target in 2001. Research on ¹⁷⁷Lu has demonstrated its immense potential in radiotherapeutic applications, a direct outcome of which has resulted in indigenous development of two agents viz.¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-DOTA-TATE presently being evaluated in human patients for palliative care of bone pain due to skeletal metastases and treatment of malignancies of neuroendocrine origin, respectively. Using locally produced ¹⁷⁷Lu, the radiolabeling of a plethora of other molecules with potential applicability in radiation synovectomy and targeted therapy of malignant tumors have been successfully demonstrated. A few of these agent such as a novel ¹⁷⁷Lu-labeled porphyrin has shown considerable promise in initial studies and is presently evaluated. In the present article, our research efforts toward standardization of production methodology of ¹⁷⁷Lu in high specific activity and its utilization in the devel opment of agents for targeted radiotherapy are being reported.