Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma

Kim A. Selting, Jaime Simon, Jim C. Lattimer, Alan Ketring, Sandra Axiak-Bechtel, Keith Frank, Richard E. Wendt, Jeffrey N. Bryan, Deborah Tate, Charles Maitz, Joni Lunceford, Lindsay Donnelly, Kevin Keegan, Carolyn J. Henry

Research output: Contribution to journalArticlepeer-review


153Sm-DOTMP (CycloSam®) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%–60% decrease) was equivocal in three dogs, and worsened in four dogs (66%–115% increase); two dogs were not evaluable. Repeat 18F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

Original languageEnglish (US)
Pages (from-to)982-991
Number of pages10
JournalVeterinary Radiology and Ultrasound
Issue number5
StatePublished - Sep 2023
Externally publishedYes


  • bone cancer
  • canine
  • radioisotope
  • skeletal targeted radiotherapy

ASJC Scopus subject areas

  • General Veterinary


Dive into the research topics of 'Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma'. Together they form a unique fingerprint.

Cite this