A "mix-and-use" approach for formulation of human clinical doses of 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-DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of Lu 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-DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of Lu-DOTMP was developed, which involves simple mixing of approximately 3.7 GBq of Lu activity as LuCl solution to an aqueous solution containing 5 mg of DOTMP and 8 mg of NaHCO . The proposed protocol yielded Lu-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 activity and would thereby accelerate the clinical translation of Lu-DOTMP.