title: 177Lu-EDTMP: a viable bone pain palliative in skeletal metastasis.
abstract: Designing ideal radiopharmaceuticals for use as bone pain palliatives require the use of a moderate energy beta() emitter as a radionuclide and a suitable polyaminophosphonic acid as a carrier molecule. Owing to its suitable decay characteristics [T(1/2) = 6.73 d, E((max)) = 497 keV, E() = 113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production in adequate specific activity and radionuclidic purity using a moderate flux reactor, 177Lu could be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study was therefore, oriented toward the preparation and biologic evaluation of 177Lu complex of ethylenediaminetetramethylene phosphonic acid (EDTMP) in various animal models, with an aim to prepare a viable radiopharmaceutical for bone pain palliation. 177Lu was produced with a specific activity of approximately 12 GBq/mg (approximately 324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu2O3 targeted at a thermal neutron flux of approximately 6 x 10(13) n/cm(2).s for 21 days. 177Lu-EDTMP complex was prepared in high-yield and excellent radiochemical purity (>99%), using EDTMP synthesized and characterized in-house. The complex exhibited excellent in vitro stability at room temperature. Biodistribution studies in Wistar rats showed a rapid skeletal accumulation of injected activity [(1.74 +/- 0.30)% per gram in femur at 3 hours postinjection] with a fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic imaging studies carried out in normal Wistar rats, New Zealand white rabbits, as well as in Beagle dogs also demonstrated significant accumulation of the agent in the skeleton and almost no retention of activity in any other vital organs.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Lajos
authors.initials: L
authors.lastname: Balogh
authors.forename: Pradip R
authors.initials: PR
authors.lastname: Chaudhari
authors.forename: Haladhar D
authors.initials: HD
authors.lastname: Sarma
authors.forename: András
authors.initials: A
authors.lastname: Polyák
authors.forename: Domokos
authors.initials: D
authors.lastname: Máthé
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
authors.forename: Gyõzõ
authors.initials: G
authors.lastname: Janoki
authors.forename: Maroor R A
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D004285:Dogs; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000532:radiotherapy*; D010166:Palliative Care; D011817:Rabbits; D011859:Radiography; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C119503:lutetium ethylenediaminetetramethylene phosphonic acid