PRECLINICAL EVALUATION OF 117mSn COLLOID AS A RADIOSYNOVIORTHESIS
PRECLINICAL EVALUATION OF 117mSn COLLOID AS A RADIOSYNOVIORTHESIS AGENT FOR TREATMENT OF CANINE ELBOW JOINT OSTEOARTHROSIS J. LATTIMER1, K. SELTING1, J. LUNCEFORD1, J. HOLLAND1, J. SIMON2, N. STEVENSON3, C. DOERR3, J. DONECKER3 1 University of Missouri, Columbia Missouri 65211 2 Isotherapeutics Group, Angleton TX 77515 3 Convetra, Inc., The Woodlands, TX 77380 Disclosure: The work in this project was supported by a contract between
Convetra, Inc. and the University of Missouri. Osteoarthrosis/Osteoarthritis Most common clinical disorder Result of joint injury Trauma Instability Infection bacterial, viral, rickettsial Autoimmune disease Osteoarthrosis/Osteoarthritis Most common clinical disorder Progression
Synovial inflammation earliest stage of joint degeneration Ligamentous Cartilage and capsular injury injury Subchondral of disease and perichondral bone injury latest stage Progression rate Radiosynoviorthesis
Use of a radioisotope preparation to partially ablate the synovium and reduce inflammation in a joint thereby slowing progression of osteoarthritis Challenges Retention of the isotope in the joint tissues Minimal intrinsic chemical toxicity to joint structures Minimal radiation dose to cartilage, bone and ligaments/tendons Minimize
radiation dose to rest of patient and others 117m Sn Colloid (Synovetin OA) Half-life 14 days Emissions Conversion electrons 140 keV <300 micron range in tissue Insufficient energy to reach bone and tendons
Gamma photons 158 keV imageable on gamma camera Colloid size - ~(3 15 m) Promotes retention in joint through engulfment by joint macrophages Stable in suspension for 5 weeks Easily suspended and injected Prior studies Prior studies performed in rats Lewis
rat meniscal tear model > 150 rats A range of doses were treated Duration of trial was 42 days Confirmed Minimal No > decrease in inflammation adverse effects on synovium except high dose group cartilage, bone or ligamentous injury 99% of isotope retained in the joint
Study design Five young adult purpose-bred female hounds Minimum 5 days acclimation CBC, serum chemistries, urinalysis Radiographs, PET/MRI, post injection nuc. med. scan Joint fluid cytology and analysis
Injection of left elbow with 117mSn colloid 2.5 millicuries normalized to 22.75 kg BW by BSA Daily observation for lameness Study Design Continued 24 hours after injection NM scan of elbow and abdomen Collection of blood, urine and feces for 5 days Standard size samples counted in swipe counter
Total excreted urine and feces activity calculated 42 days after injection - all clinical pathology and imaging studies repeated 43 days after injection euthanasia & postmortem All major organs collected and counted for total activity Histopathology of all major organs
Histopathology and autoradiography of joint tissues Results No NM dog exhibited any lameness after injection confirmed retention in joint at 24 hours Urine and feces collection indicated > 99% average retention Imaging Post studies were normal and static between studies mortem studies Organ
No and elbow activity indicated > 99% retention in elbow histologic abnormalities were found in organs or joints Micro autoradiography confirmed synovial localization PET/MRI images day 0 & 42 Post mortem autoradiography of synovium Conclusions Sn colloid (Synovetin) should be evaluated as a radiosynoviorthesis agent in dogs 117m It
was retained in the elbow joints with > 99% localization The No agent was well tolerated by the animals adverse reactions to the injection were detected Further trials in dogs with naturally occurring clinical arthritis are needed to evaluate the efficacy of this agent Future Studies Sn colloid (Synovetin) is currently being evaluated in a multicenter trial for treatment of clinical lameness in dogs with grade 1 or 2 elbow arthritis. 117m
Trials are currently being planned for evaluation of this agent in the treatment of osteoarthritis in a limited equine study. Evaluation of efficacy in other joints and more advanced osteoarthritic conditions in dogs References: The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis, Sellam, J. & Berenbaum, F. Nat. Rev. Rheumatol. 6, 625635 (2010) New insights on cell death from radiation exposure, Kevin M Prise, Giuseppe Schettino, Melvyn Folkard, Kathryn D Held, Lancet Oncol 2005; 6: 52028
Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations, Sololove J, Lepus C; Ther Adv Musculoskel Dis, 2013 5(2) 77-94 Direct in vivo evidence of activated macrophages in human osteoarthritis, V.B. Kraus*, G. McDaniel, J.L. Huebner, T.V. Stabler, C.F. Pieper, S.W. Shipes,N.A. Petry, P.S. Low, J. Shen, T.A. McNearney, P. Mitchell, in press, Osteoarthritis and Cartilage (2016)
Bone Markings . Bone Markings may be defined in two major categories: Processes (including elevations and projections)which either form joints or serve as a point of attachment for muscles, tendons, or ligaments.
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