A “mix‐and‐use” approach for formulation of human clinical doses of 177 177 Lu‐DOTMP Lu‐DOTMP at hospital radiopharmacy for management of pain arising from skeletal metastases

摘要

Use of bone‐seeking radiopharmaceuticals is an established modality in the palliative care of pain due to skeletal metastases. 177 Lu‐DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of 177 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 177 Lu‐DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of 177 Lu‐DOTMP was developed, which involves simple mixing of approximately 3.7?GBq of 177 Lu activity as 177 LuCl 3 solution to an aqueous solution containing 5?mg of DOTMP and 8?mg of NaHCO 3 . The proposed protocol yielded 177 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 177 Lu activity and would thereby accelerate the clinical translation of 177 Lu‐DOTMP.