Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

Abstract

Sandra M Axiak-Bechtel,1 Anandhi Upendran,2,3 Jimmy C Lattimer,1 James Kelsey,3,4 Cathy S Cutler,4 Kim A Selting,1 Jeffrey N Bryan,1 Carolyn J Henry,1,5 Evan Boote,6 Deborah J Tate,1 Margaret E Bryan,7 Kattesh V Katti,3,8 Raghuraman Kannan3,8 1Department of Veterinary Medicine and Surgery, 2Department of Physics, University of Missouri, Columbia, MO, USA; 3Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA; 4Missouri University Research Reactor, 5Department of Internal Medicine, University of Missouri, Columbia, MO, USA; 6Spectrum Health, Grand Rapids, MI, USA; 7Department of Statistics, 8Department of Radiology, University of Missouri, Columbia, MO, USA Introduction: Gum arabic-coated radioactive gold nanoparticles (GA-198AuNPs) offer ­several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-198AuNPs injected intralesionally. We proposed that a single treatment of GA-198AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity.Methods: Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection.Results: No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and urethra; no systemic uptake was detected.Conclusion: GA-198AuNP therapy had no short-term toxicity in the treatment of prostatic cancer. While therapeutic agent was found in the prostate immediately following injection, some loss of agent was detected in the bladder and urethra. Localization of radioactivity within the prostate was lower than anticipated and likely due to normal vestigial prostatic ducts. Therefore, further study of retention, dosimetry, long-term toxicity, and efficacy of this treatment is warranted prior to Phase I trials in men. Keywords: brachytherapy, prostatic cancer, safety trial