Inhibiting ERK1/2 signaling resulted in osteosarcoma cell death by upregulating pro-apoptotic genes and inhibiting the Bcl-2-mediated resistance to doxorubicin. In osteosarcoma-bearing mice, ERK1/2 targeting alone or in combination with doxorubicin prolonged survival as compared with untreated mice.

This investigation reports the preparation of agglomerated Fe 3 O 4 nanoparticles and evaluation of its utility as a viable carrier in the preparation of radiolanthanides as potential therapeutic agents for the treatment of arthritis. The material was synthesized by a chemical route and characterized by XRD, FT-IR, SEM, EDX and TEM analysis. The surface of agglomerated particle possessed ion pairs (-O À :Na + ) after dispersing particles in a NaHCO 3 solution at pH = 7 which is conducive for radiolanthanide (*Ln = 90 Y, 153 Sm, 166 Ho, 169 Er, 177 Lu) loading by replacement of Na + ions with tripositive radiolanthanide ions. Radiolanthanide-loaded particulates exhibited excellent in vitro stability up to B3 half-lives of the respective lanthanide radionuclides when stored in normal saline at 37 1C. The radiochemical purities of the loaded particulates were found to be retained to the extent of 470% after 48 h of storage when challenged by a strong chelator DTPA present at a concentration as high as 5 mM, indicating fairly strong chemical association of lanthanides with agglomerated Fe 3 O 4 nanoparticles. Biodistribution studies of 90 Y and 166 Ho-loaded particulates carried out after intra-articular injection into one of the knee joints of a normal Wistar rat revealed near-complete retention of the radioactive preparations (498% of the administered radioactivity) within the joint cavity even after 72 h post injection. This was further confirmed by sequential whole-body radio-luminescence imaging. These experimental results are indicative of the potential use of radiolanthanide-loaded agglomerated Fe 3 O 4 nanoparticles for the treatment of arthritis.

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.

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