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

Abstract

Introduction 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. Conclusion 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.

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

“…Therefore, it is generally considered biocompatible and has been used in some routine clinical practices for many years (e.g., in treating rheumatoid arthritis). Several studies have reported no significant short-term toxicity of AuNPs (1 day to 3 months) (23)(24)(25). You et al (26) have reported a lack of both acute and chronic toxicity over 3 months following multiple injections of PEGylated hollow gold nanospheres in mice.…”

Renaissance of nuclear medicine through green nanotechnology: functionalized radioactive gold nanoparticles in cancer therapy—my journey from chemistry to saving human lives

“…Overall, these studies have revealed that the utility of BED of 105 Gy of GAP-198AuNPs in prostate tumor bearing dogs had no short-term toxicity in the treatment of prostatic cancer. Combination of imaging modalities (CT/SPECT) revealed that the GAP-198AuNP therapeutic agent was found localized in the prostate immediately following injection, with some loss of the agent detected in the bladder and urethra [34]. The in vivo studies also revealed that the overall localization of Au-198 radioactivity within the prostate was lower than anticipated presumably due to normal vestigial prostatic ducts while no systemic toxicity was noted [34].…”

“…Recently, our collaborator Bechtel et al has completed a comprehensive investigation on the tolerance and toxicity studies of gum arabic-functionalized radioactive gold nanoparticles GAP-198-AuNPs [34]. This is the first ever detailed in vivo investigation in a human mimicking prostate cancer disease model.…”

“…Combination of imaging modalities (CT/SPECT) revealed that the GAP-198AuNP therapeutic agent was found localized in the prostate immediately following injection, with some loss of the agent detected in the bladder and urethra [34]. The in vivo studies also revealed that the overall localization of Au-198 radioactivity within the prostate was lower than anticipated presumably due to normal vestigial prostatic ducts while no systemic toxicity was noted [34]. A quick comparison of in vivo retention of data for GAP-198AuNPs and EGCG-198-AuNPs reveals that the laminin receptor affinity of EGCG promotes significant accumulation and retention of Au-198 radioactivity within prostate tumors in mice as compared to similar data for the non-specific GAP-198AuNPs agent.…”

Preparation and characterization of chitosan-capped radioactive gold nanoparticles: neutron irradiation impact on structural properties

“…The radioisotope of gold-198 with a half-life of 2.7 days can generate a β-particle with a maximum energy of 960 keV (99 %) suitable for therapeutic applications and a 412 keV (95.6 %) γ-ray for gamma imaging or single photon emission computed tomography (SPECT). In recent years, nanoparticles based on β-emitter radioisotopes of gold appear to be a promising approach for improved cancer treatment [11][12][13][14][15]. Surface engineering of nanoparticles plays a major role in their colloidal stability and biological properties [16].…”