PRECLINICAL EVALUATION OF 117mSn COLLOID AS A RADIOSYNOVIORTHESIS

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)

Recently Viewed Presentations

  • Foundations of Structural Kinesiology

    Foundations of Structural Kinesiology

    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.
  • ...and they all fall Down!

    ...and they all fall Down!

    I believe that this will occur because I think that the dominoes with less space in between them will pick up more momentum as they fall. Specifically, I think that the domino chain with 0.5 cm separating each domino will...
  • Politics and Political Participation - SSCC - Home

    Politics and Political Participation - SSCC - Home

    Politics and Political Participation Theory And ... racial formation Race and ethnicity as one dimension of inequality Immigration and globalization have enabled individuals to maintain ties with their home countries and ethnic groups National Context: cultural and ethnic inclusiveness and...
  • The Strongest One Vocabulary - Jefferson County Schools, TN

    The Strongest One Vocabulary - Jefferson County Schools, TN

    The Strongest One Vocabulary Second Grade Reading Vocabulary dangerous gnaws narrator relatives dangerous Not safe. gnaws Biting and wearing away by biting. narrator A person who tells a story or play. relatives The people who belong to the same family...
  • Hess&#x27;s Law and enthalpy of reaction

    Hess's Law and enthalpy of reaction

    Hess's Law. Hess's law states that "[i]f a reaction is carried out in a series of steps, H. for the overall reaction will be equal to the sum of the enthalpy changes for the individual steps."
  • Exam Revision for Paper 2 Option B4. Elizabeth Section ...

    Exam Revision for Paper 2 Option B4. Elizabeth Section ...

    Exam Revision for Paper 2 Option 2B.Elizabeth 1558 - 1588- Depth Study . AIM - To be fully prepared for the second section of Paper 2. 1 hr 45 minutes. 40% of final mark
  • FREE BODY DIAGRAM FBD - UCF Physics

    FREE BODY DIAGRAM FBD - UCF Physics

    Draw these forces as arrows with tails at the dot (object). ... Hence Fx = 12 N and Fy = 0 N The net force F : the y component is zero because the normal Force and the weight cancel....
  • Hubbert&#x27;s Peak, The Coal Question, and Climate Change Dave ...

    Hubbert's Peak, The Coal Question, and Climate Change Dave ...

    Wallace Pratt had published an estimate of his own and also a questionnaire he had sent to 25 members of the petroleum industry he regarded as especially well informed. Out of this he got 22 replies. Of all of them,...