title: Preparation, evaluation, and first clinical use of 177Lu-labeled hydroxyapatite (HA) particles in the treatment of rheumatoid arthritis: utility of cold kits for convenient dose formulation at hospital radiopharmacy.
abstract: While radiation synovectomy (RSV) constitutes a successful paradigm for the treatment of arthritis, a major cornerstone of its success resides in the selection of appropriate radiolabeled agent. Among the radionuclide used for RSV, the scope of using (177)Lu [T1/2  = 6.65 d, Eβ(max)  = 497 keV, Eγ  = 113 KeV (6.4%), 208 KeV (11%)] seemed to be attractive owing to its suitable decay characteristics, easy availability, and cost-effective production route. The present article describes a formulation of (177)Lu-labeled hydroxyapatite (HA) using ready-to-use kits of HA particles of 1-10 µm size range. The developed kits enable convenient one-step preparation of (177)Lu-HA (400 ± 30 MBq doses) in high radiochemical purity (>99%) and stability at hospital radiopharmacy. The preparation showed promising results in pre-clinical studies carried out in Wistar rats bearing arthritis in knee joints. In preliminary clinical investigation, significant improvement in the disease conditions was reported in 10 patients with rheumatoid arthritis of knee joints treated with 333 ± 46 MBq doses of (177)Lu-HA. The studies reveal that while (177)Lu labeled HA particles holds considerable promise as a cost-effective agent for RSV, the adopted strategy of using HA kits could be a potential step toward wider clinical utilization of radiolanthanide-labeled HA particles.
authors: Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: Sudipta
authors: S
authors: Chakraborty
authors: K V
authors: KV
authors: Vimalnath
authors: A
authors: A
authors: Rajeswari
authors: Ajit
authors: A
authors: Shinto
authors: H D
authors: HD
authors: Sarma
authors: K
authors: K
authors: Kamaleshwaran
authors: P
authors: P
authors: Thirumalaisamy
authors: Ashutosh
authors: A
authors: Dash
mesh_terms: D000328:Adult; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D006882:Hydroxyapatites / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007553:Isotope Labeling; D007719:Knee Joint / Q000000981:diagnostic imaging; D008187:Lutetium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D006882:Hydroxyapatites; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium
keywords: 177Lu; hydroxyapatite; kit formulation; pain score; radiation synovectomy (RSV); rheumatoid arthritis (RA)