Affiliation:
1. Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia Missouri USA
2. IsoTherapeutics Group LLC Angleton Texas USA
3. Department of Imaging Physics The University of Texas M.D. Anderson Cancer Center Houston Texas USA
4. Department of Medicine Division of Internal Medicine University of Missouri Columbia Missouri USA
Abstract
Abstract153Sm‐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.
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