A "mix-and-use" approach for formulation of human clinical doses of 177 Lu-DOTMP at hospital radiopharmacy for management of pain arising from skeletal metastases.

Use of bone-seeking radiopharmaceuticals is an established modality in the palliative care of pain due to skeletal metastases. Lu-177-DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of Lu-177 and excellent thermodynamic stability and kinetic rigidity of the macrocyclic complex. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of clinical doses of Lu-177-DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of Lu-177-DOTMP was developed, which involves simple mixing of approximately 3.7 GBq of Lu-177 activity as (LuCl3)-Lu-177 solution to an aqueous solution containing 5 mg of DOTMP and 8 mg of NaHCO3. The proposed protocol yielded Lu-177-DOTMP with > 98% radiochemical purity, and the resultant formulation showed excellent in vitro stability and desired pharmacokinetic properties in animal model. Preliminary clinical investigations in 5 patients showed specific skeletal accumulation with preferential localization in the osteoblastic lesion sites and almost no uptake in soft tissue or any other major nontarget organ. The developed "mix-and-use" strategy would be useful for large number of nuclear medicine centers having access to Lu-177 activity and would thereby accelerate the clinical translation of Lu-177-DOTMP.