Biodistribution study of radioactive gold nanoparticles (SNBI-29) in normal beagle dogs

Objectives Radioactive gold nanoparticles (GA-198AuNP; SNBI-29) based therapeutic agent is being developed for the treatment of prostate cancer. The objective of the present study was to investigate the biodistribution of SNBI-29 following intra-prostatic injection by scintigraphic imaging.

Methods A total of 14 normal beagle dogs were recruited for the study. Intra-prostatic administration of SNBI-29 with a total dose ranging from 2.5-5mCi (105Gy BED) was performed under CT guidance. Scintigraphic images were acquired at 15min, 1h, 4h, 24h, 2d, 4d and 8d post injection time points and the dogs were euthanized after 8d to evaluate the biodistribution.

Results Maximum amount of radioactivity cleared via urine within 24 hours of injection. Scintigraphic images confirmed the clearance of SNBI-29 from the prostate in to the bladder immediately following intraprostatic administration. Scintigraphic imaging studies indicated minimal accumulation of SNBI-29 in vital organs. No measurable radioactivity was observed in blood at any time point. Interestingly, small amounts of the total injected dose (~5%) were found to be retained in the prostate after 8d post injection time point.

Conclusions The detailed biodistribution study demonstrates that intra-prostate injection of SNBI-29 results in rapid renal clearance and the dose is well-tolerated in normal dogs with no evidence of systemic toxicity. The significant radioactivity transport into the bladder is thought to be due to the presence of acini ducts found throughout the normal healthy prostate glands that are directly connected to the urethra. Further studies are important to understand the nanoparticulate characteristics of retained and cleared SNBI-29.

Research Support NIH SBIR Phase II Contract NO. HHSN261201000100C awarded to Nanoparticle BioChem, Inc., Shasun-NBI LLC, Columbia, MO-65203.