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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 60; no. 9; pp. 410 - 419
• Main Authors: Chakraborty, Sudipta, Vimalnath, K.V., Rajeswari, A., Chakravarty, Rubel, Sarma, H.D., Radhakrishnan, E., Kamaleshwaran, K., Shinto, Ajit S., Dash, Ashutosh
• Format: Journal Article
• Language: English
• Published: Bognor Regis Wiley Subscription Services, Inc 01.07.2017
• Subjects: 177Lu; Biocompatibility; Biomedical materials; clinical dose; DOTMP; In vitro methods and tests; Localization; Metastases; Metastasis; mix‐and‐use strategy; Nuclear medicine; Osteoblasts; Pain; pain palliation; Pharmaceuticals; Pharmacology; Radiochemistry; Radioisotopes; Rigidity; skeletal metastases; Stability
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3517

Use of bone‐seeking radiopharmaceuticals is an established modality in the palliative care of pain due to skeletal metastases. 177Lu‐DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of 177Lu 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 177Lu‐DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of 177Lu‐DOTMP was developed, which involves simple mixing of approximately 3.7 GBq of 177Lu activity as 177LuCl3 solution to an aqueous solution containing 5 mg of DOTMP and 8 mg of NaHCO3. The proposed protocol yielded 177Lu‐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 177Lu activity and would thereby accelerate the clinical translation of 177Lu‐DOTMP. A robust and easily adaptable protocol has been developed for formulation of clinically relevant doses of 177Lu‐DOTMP at a hospital radiopharmacy. This strategy would be useful to a large number of nuclear medicine centers having access to 177Lu activity and is expected to accelerate widespread clinical translation of 177Lu‐DOTMP.