Gum arabic-coated radioactive gold nanoparticles (GA-¹⁹⁸AuNP) are effectively retained and result in 80% tumor reduction in a mouse model of human prostatic carcinoma. Our objectives were to determine the toxicity and preliminary efficacy of GA-¹⁹⁸AuNP administered intralesionally to dogs with spontaneously occurring carcinoma of the prostate. The hypothesis was that intralesional GA-¹⁹⁸AuNP would cause short-term swelling but cause no systemic toxicity and result in tumor stabilization or shrinkage. Following Institutional Animal Care and Use Committee approval, dogs with a diagnosis of prostate carcinoma without bladder involvement were eligible for enrollment with informed owner consent. Staging was performed and injection of GA-¹⁹⁸AuNP was achieved with CT guidance (100–200 µL per site in multiple sites, total amount varied based on tumor size). A complete blood count, chemistry panel, and urinalysis were performed weekly for 4 weeks following treatment; a CT scan was performed 4 weeks after treatment. Nuclear scintigraphy was performed regularly (15 minutes, 1 h, 4 h, 1, 2, 4, and 5 days post-injection) to determine the degree of retention of GA-¹⁹⁸AuNP in the prostate. Following the 4-week trial period, chemotherapy could be started at the discretion of the pet owner. Twenty-two dogs were enrolled; 3 dogs had metastasis to the lymph nodes in the sublumbar region, and 19 dogs had no evidence of metastasis. Two dogs were treated to a biologically equivalent dose of 50 Gy, and 20 dogs were treated to 105 Gy. One dog died 12 days post injection due to urethral obstruction from either tumor swelling or disease progression. Following this event, dogs with evidence of urethral obstruction had urethral stents placed (n=15) prior to treatment. Fifteen dogs received chemotherapy. The median survival time of dogs receiving chemotherapy was 132 days (range 55–420 days) compared to 56 days (range 12–255 days) in dogs that did not. The average tumor retention of GA-¹⁹⁸AuNP was 70% at 5 days post-injection; loss occurred into the urine through the bladder. No accumulation of dose was found in heart, lung, liver, spleen, and kidney as determined by whole body planar imaging up to 5 days post-treatment. The median reduction in tumor volume was 10% one month after GA-¹⁹⁸AuNP therapy in 14 dogs. In conclusion, intratumoral administration of GA-¹⁹⁸AuNP caused no acute systemic toxicities in any dog and may be effective in decreasing tumor size; however, local tumor swelling is possible, and dogs must be closely monitored for evidence of urethral obstruction.

Disclosures

Disclosures to report
Grant and financial support: This work was supported by a grant from the University of Missouri Institute of Clinical and Translational Sciences, NIH-SBIR Phase II contract (HHSN261201000100C), and Shasun NBI, LLC. AU, KVK and RK are co-founders of Nanoparticle Biochem, Inc.