Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer.
BACKGROUND
Gum arabic-coated radioactive gold nanoparticles (GA-(198)AuNPs) 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-(198)AuNPs injected intralesionally. We proposed that a single treatment of GA-(198)AuNPs 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.


CONCLUSIONS
GA-(198)AuNP 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.
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA.
Sandra M
SM
Axiak-Bechtel
Department of Physics, University of Missouri, Columbia, MO, USA ; Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA.
Anandhi
A
Upendran
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA.
Jimmy C
JC
Lattimer
Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA ; Missouri University Research Reactor, Columbia, MO, USA.
James
J
Kelsey
Missouri University Research Reactor, Columbia, MO, USA.
Cathy S
CS
Cutler
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA.
Kim A
KA
Selting
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA.
Jeffrey N
JN
Bryan
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA ; Department of Internal Medicine, University of Missouri, Columbia, MO, USA.
Carolyn J
CJ
Henry
Spectrum Health, Grand Rapids, MI, USA.
Evan
E
Boote
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA.
Deborah J
DJ
Tate
Department of Statistics, University of Missouri, Columbia, MO, USA.
Margaret E
ME
Bryan
Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA ; Department of Radiology, University of Missouri, Columbia, MO, USA.
Kattesh V
KV
Katti
Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA ; Department of Radiology, University of Missouri, Columbia, MO, USA.
Raghuraman
R
Kannan
D000818:Animals; D001918:Brachytherapy; D004285:Dogs; D006046:Gold / Q000627:therapeutic use / Q000633:toxicity*; D006170:Gum Arabic / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy* / Q000662:veterinary; D014057:Tomography, X-Ray Computed
D006046:Gold; D006170:Gum Arabic
brachytherapy; prostatic cancer; safety trial