In vivo evaluation of gum arabic stabilized gold-199 nanoparticles in normal dogs

Objectives Investigate diffusion pattern of gum arabic stabilized radioactive gold nanoparticles (GA-¹⁹⁹AuNPs), in prostate glands and monitor subsequent distribution to other organs following intra-prostate administration in normal dogs.

Methods H¹⁹⁹AuCl₄ was prepared from ¹⁹⁹Au produced at MURR, following n-irradiation of ¹⁹⁸Pt, and used to prepare GA-¹⁹⁹AuNPs as previously reported. The UV-Vis spectrum showed characteristic surface plasmon resonance peak in the 529-535 nm region and Radio-TLC confirmed that over 99% of ¹⁹⁹Au was present as the nanoparticulate form. Approximately 1.2 mCi (44.4 MBq) of GA-¹⁹⁹AuNPs was injected directly into the prostate glands of two normal beagle dogs (11 - 20 Kg). Serial planar scintigraphic images were performed at 15 min, 1 h, 4 h, 1, 2, 4 and 8 d post injection along with calibrated standards. The distribution of GA-¹⁹⁹AuNPs in major organs (heart, lung, liver, kidney, spleen, and prostate) was assessed with NaI- detection following necropsy. Dogs were euthanized on day 8 and excised prostate gland was analyzed by autoradiography and histology studies.

Results No localization of GA-¹⁹⁹AuNPs in organs other than the prostate gland was detectable over the 8 d imaging protocol. However, some initial leakage into the urethra was detected. Autoradiography of slices from the prostate glands demonstrated significant diffusion and retention of the GA-¹⁹⁹AuNPs within the prostate capsule. The counts in sections of all other excised organs were minimal.

Conclusions GA-¹⁹⁹AuNPs remain trapped in the prostate capsule for at least 8 days and exhibit minimal localization in other organs due to leakage. Uniform diffusion indicates delivery of a homogeneous radiation dose to prostate cancer cells located within the capsule and is consistent with preliminary therapeutic studies conducted in client owned dogs with spontaneous prostate cancer.

Research Support NCI/NIH SBIR Phase II Contract No. HHSN261201000100C ; NCI control No. N44-C0-201000100 awarded to Nanoparticle BioChem, Inc