Abstract View
Separation of 211At with the use of functionalized gold nanoparticles (AuNPs)
Category: Other Halogen Radionuclide Chemistry
Authors:
Shayden Fritz1,2, Elizabeth Schnorrenberg1,2, Alexandra Tabacaru1,2, Gabriel Tabacaru2, Christine Lawrence2, Lauren McIntosh2, Sherry J. Yennello1,2
1. Department of Chemistry, Texas A&M University, College Station TX USA; 2. Cyclotron Institute, Texas A&M University, College Station TX USA
Objective: A radionuclide of interest for targeted alpha therapy (TAT) is astatine-211 that has a 7.2 hour half-life. Following the irradiation of a bismuth target, the target is dissolved with nitric acid creating a solution with bismuth and astatine. Gold nanoparticles (AuNPs) offer a promising approach for isolating astatine-211 from this mixture, and then can be further processed for drug delivery applications.
Methods: AuNPs were synthesized at various sizes and functionalized with either thiol-polyethylene glycol-amine ( HS-PEG-NH2) or thiol-polyethylene glycol (HS-PEG) prior to astatine attachment. The extent of separation of astatine from the bismuth solution and attachment to the AuNPs was determined with an HPGe by detection of the gamma ray emitted during the decay of 211At, the samples were measured before and after separation from the nitric media (Fig. 1A). The oxidation states of the astatine can be modified with the use of hydroxylamine as a reductant following separation by a 3-octanone column The oxidation states are likely astatide in the hydroxylamine and AtO+ in the 3-octonone. Additionally, the astatine in various oxidation states were tested for attachment efficiency. The stability of the complexes was tested with a strong reducing agent (hydrazine) at various concentrations, and a time trial completed in biological media. After the separation process, targeting agents can be functionalized onto the 211At-AuNPs complexes for cytotoxicity studies (Fig. 1B).
Results: The 211At in the bismuth-acidic solution showed high affinity for the AuNPs with nearing 100% uptake of the 211At on the complexes at low AuNP concentrations (Fig. 1C). The astatine in various oxidation states showed a 20% uptake of the astatine in the AtO+ form, and a 95% uptake in the astatide form. The attempt to remove 211At with hydrazine showed no removal of astatine at low to moderate concentrations of hydrazine, however at 16.5M hydrazine a 25% removal of 211At was observed. This shows strong stability of the complexes in harsh conditions. In addition, due to the half-life of astatine, quick attachment is necessary for drug delivery purposes. Therefore, time trials were completed and showed no significant loss in astatine within 24h of the attachment in biological media, indicating the high potential for drug delivery. The AuNP-PEG-RGD complexes showed no toxicity at concentrations between 0.1ppm to 250ppm. There was an increase in cytotoxic activity found with an increase in the 211At concentration.
Conclusion: Due to the high affinity astatine has been found to have with gold, gold nanoparticles allow for selective binding of astatine to the nanoparticles surface enabling for the separation of astatine from the bismuth-nitric matrix. The functionalized AuNPs have high stability in the acidic conditions, and show strong stability with 211At allowing the complexes to be used for drug delivery purposes. Once isolated, the complexes can be easily functionalized with a variety of targeting agents for therapeutic application. This approach will enable a versatile platform for TAT with astatine.
Figure 1. (A) Structure of the AuNP complexes with the two functionalization used for separation of the 211At from the bismuth-acidic matrix; B) Structure of the 211At-AuNP-PEG-RGD complexes for drug delivery; C) Various concentration of the functionalized AuNPs with percent uptake of 211At.