Preparation of Rh[16aneS₄-diol]²¹¹At and Ir[16aneS₄-diol]²¹¹At Complexes as Potential Precursors for Astatine Radiopharmaceuticals. Part I: Synthesis

Abstract

The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with 211 At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different 211 At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of 211 At − and *I − (*I = 131 I or 125 I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS 4 -diol) ligand. Radioactive *I − anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with 211 At. Four complexes Rh[16aneS 4 -diol]*I/ 211 At and Ir[16aneS 4 -diol] *I/ 211 At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS 4 -diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS 4 -diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1-1.5 h at 75-80 °C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS 4 -diol] 131 I and Ir[16aneS 4 -diol] 131 I complexes were obtained after only 20 min exposure of the reaction mixtures to microwave radiation. In conclusion, this study has shown that it is possible to attach an astatide anion to soft metal cations in a simple and fast one-step procedure, with high yields. These complexes will be evaluated as reagents for labeling biomolecules.

Gold nanoparticle bioconjugates labelled with 211At for targeted alpha therapy

“…The internalization studies were performed using AuNPs and AuNPs-SP (5)(6)(7)(8)(9)(10)(11) I-AuNPs-SP(5-11). Aer treatment, the growth medium of each well was collected, the cells were washed twice with 750 mL of PBS and incubated with 500 mL of pre-warmed trypsin solution at 37 C for 10 min.…”

“…The biologically active fragment of Substance P(5-11), named shortly as SP (5)(6)(7)(8)(9)(10)(11), was conjugated to the gold nanoparticles to obtain bioconjugates targeting NK1 receptors on glioma cells. Previously it was found that Substance P in cerebrospinal uid exhibits a stability of 84% aer 24 hours, while the serum residence time is only 1 to 2 minutes due to the rapid degradation.…”

“…3. The transmission electron micrograph of AuNPs-S-PEG-Substance P (5)(6)(7)(8)(9)(10)(11) shows that the particles are uniformly dispersed with signicantly narrow size equal to 5 nm and to 15 nm (Fig. 3).…”

Medical Radioisotopes Produced Using the Alpha Particle Beam from the Warsaw Heavy Ion Cyclotron

“…The determined thick target yields and saturation yields for the 43 Sc and 44 Sc radioisotopes are shown in Table. Figure 3 shows the radionuclidic purity of 43 Sc as a function of time after the EOB. 211 At [17,8], the adsorption of 211 At on silver impregnated TiO 2 nanoparticles [5] and recently adsorption on gold nanoclusters and nanoparticles [18]. The radiobioconjugates obtained exhibited good stability in various biological liquids including human serum and cerebral spinal uid.…”

Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

“…These indirect methods link radio-metals to proteins using bifunctional chelators [BFCs]. As their name already indicates, these molecules consists of two functional groups which serve different purposes; one functional group for the binding to the protein and a chelating unit which carries the radionuclide [70,71]. A BFC is essentially made up of three sections, a radionuclide binding unit, a unique ligand framework and a conjugating group for attachment to the antibody [72].…”