Trastuzumab-Modified Gold Nanoparticles Labeled with 211At as a Prospective Tool for Local Treatment of HER2-Positive Breast Cancer.

Highly localized radiotherapy with radionuclides is a commonly used treatment modality for patients with unresectable solid tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This uses local intratumoral injection of 5-nm-diameter gold nanoparticles (AuNPs) labeled with an α-emitter (211At), modified with polyethylene glycol (PEG) chains and attached to HER2-specific monoclonal antibody (trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of gold for heavy halogens, the bioconjugate was labelled with 211At obtained by α irradiation of the bismuth target. The labeling yield of 211At was greater than 99%. 211At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that 211At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that 211At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the 211At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.

211At labeled substance P (5-11) as potential radiopharmaceutical for glioma treatment.

INTRODUCTION: The purposes of the present work were to label substance P (5-11) with 211At using a rhodium(III) complex with a bifunctional ligand-2-(1,5,9,13-tetrathiacyclohexadecan-3-yloxy)acetic acid ([16aneS4]-COOH) and to assess the in vitro stability and toxicity of the obtained radiobioconjugate. METHODS: Two approaches were evaluated to obtain 131I/211At-Rh[16aneS4]-SP5-11 radiobioconjugates, based on 2-step and 1-step syntheses. In the first method 131I/211At-Rh[16aneS4]-COOH complexes were obtained that required further coupling to a biomolecule. In the second approach, the bioconjugate [16aneS4]-SP5-11 was synthesized and further labeled with 131I and 211At through the utilization of a Rh(III) metal cation bridge. The synthesized compounds were analyzed by HPLC, TLC and paper electrophoresis. RESULTS: The 131I/211At-Rh[16aneS4]-COOH complexes were obtained in high yield and possessed good stability in PBS and CSF. Preliminary studies on coupling of 131I-Rh[16aneS4]-COOH to substance P (5-11) in 2-step synthesis showed that this procedure was too long with respect to 211At half-life, prompting us to improve it by finally using a 1-step synthesis. This strategy not only shortened the labeling time, but also increased final yield of 131I/211At-Rh[16aneS4]-SP5-11 radiobioconjugates. The stability of both compounds in PBS and CSF was high. Toxicity studies with the 211At-Rh[16aneS4]-SP5-11 demonstrated that radiobioconjugate significantly reduced T98G cell viability in a dose dependent manner reaching 20% of survival at the highest radioactivity 1200kBq/mL. CONCLUSIONS: The radiobioconjugate 211At-Rh[16aneS4]-SP5-11 revealed its potential in killing glioma T98G cells during in vitro studies; therefore further animal studies to are required to determine its in vivo stability and treatment potential in normal and xenografted mice.

Combined, sequential procedure for determination of 137Cs, 40K, 63Ni, 90Sr, 230,232Th, 234,238U, 237Np, 238,239+240Pu and 241Am applied for study on contamination of soils near Zarnowiec Lake (northern Poland).

The paper summarizes results of investigation of the current state of radioactive contamination on site being under consideration for planned nuclear power plant in northern Poland. Thanks to use of sequential procedure it was possible to determine activity concentrations for radioisotopes of nine elements, both natural and artificial. Results show that observed levels of radioactive contamination are rather typical for central Europe and global fallout is dominant factor of presence of artificial radionuclides. The total deposition for artificial radionuclides revealed maxima equal to 1747 ± 121 Bq/m2 for 137Cs, 3854 ± 158 Bq/m2 for 90Sr, 101 ± 23 mBq/m2 for 237Np, 57.7 ± 6.0 Bq/m2 for 241Am, 3.27 ± 0.80 Bq/m2 for 238Pu and 68.5 ± 5.0 Bq/m2 for 239+240Pu.