Preliminary evaluation of a broad-scope tumor targeting alkylphosphocholine chelate in canines with spontaneous tumors.

403 Objectives: Despite their usefulness in cancer research, murine cancer models pose several limitations in predicting drug activity in the clinical setting. Companion canines with spontaneous cancer are advantageous since they more closely mimic the incidence, progression, and response to therapies of human cancers and unlike many rodent models, have intact immune systems. The goal of this study was to evaluate the properties of our pan-cancer targeting theranostic radiolabeled alkylphosphocholine, NM600, using the isotope pair [86Y] for PET imaging and [90Y] for therapy in canine patients bearing spontaneous tumors. Methods: Two companion canines, a 45 kg mastiff (Rex) and an 18 kg cocker spaniel (Max) presented with metastatic osteosarcoma and melanoma, respectively, were recruited through the UW-Madison Veterinary Oncology Clinic. Clinical examination at enrollment included complete blood count (CBC), urinalysis, and comprehensive metabolic panel (CMP). A [86Y]Y-NM600 185 MBq (5 mCi) intravenous bolus was administered followed by longitudinal PET/CT acquisitions at 2, 24, and 48h post-injection using a GE D710 clinical scanner. Blood samples were collected prior to each imaging timepoint to quantify blood activity and assess kinetics of [86Y]Y-NM600. Region-of interest analysis of the PET images was performed to determine [86Y]Y-NM600 uptake and clearance in tumor and normal tissues, and to estimate the dosimetry of therapeutic [90Y]Y-NM600. Conservative injected activities of 592 MBq (16 mCi) and 319 MBq (8.6 mCi) [90Y]Y-NM600 were administered to Rex and Max, respectively and clinical examination, CBC, urinalysis, and CMP were performed at regular timepoints after the administration of both the imaging and targeted radionuclide therapy agents. Results: Marked uptake and prolonged retention of [86Y]Y-NM600 in both primary and metastatic lesions were observed via serial PET/CT. Mean (max) SUV in the tumor was 4.6 (7.6) for Rex and 3.2 (4.9) for Max, peaking at 48 h post-injection for both patients. Similarly, tumor- to-muscle (T/M) uptake ratios peaked at 48 hours for both Rex and Max: 4.02 and 4.32, respectively. Blood circulation and hepatobiliary excretion of the radiotracer was evidenced by the initially elevated blood radioactivity with gradual distribution to the gallbladder and feces. Patient-specific dosimetry was performed using a voxel-based dose calculation platform that found a tumor-to-bone marrow dose ratio of greater than 2, for both the primary and the lung metastatic lesions. Administration of [90Y]Y-NM600 activity did not cause any acute and sub-acute adverse events (AEs). Serial CBC, CMP, urinalysis, and client-documented quality of life questionnaires showed no significant clinical or clinicopathologic AEs after [90Y]Y-NM600 treatment. No clinically significant changes in serum biochemistry profiles were noted, and all hematologic cell lines remained constant or higher than baseline. Conclusions: Our results demonstrate the ability of NM600 to target diverse canine tumors to safely deliver therapeutic 90Y-NM600 doses. These provide guidance for further dose escalation studies and future Phase 1 human clinical trials.