Development of thiacrown ligands for encapsulation of mercury-197m/g into radiopharmaceuticals.

The theranostic pair mercury-197m and mercury-197g (Hg, = 23.8 h/64.14 h), through their γ rays and Meitner-Auger electron emissions, have potential use as constituents in radiopharmaceuticals to treat small metastatic tumours.

The HSmacropa Series: Increasing the Chemical Softness of Hmacropa with Sulfur Atoms to Chelate Radiometals [Bi]Bi and [Pb]Pb for Radiopharmaceutical Applications.

The effects of replacing nitrogen with sulfur atoms in the 18-membered macrocycle of the Hmacropa chelator on the binding affinity and stability of "intermediate" (radio)metal [Pb]Pb and [Bi]Bi complexes are investigated. The 1,4,10,13-tetraoxo-7,16-diazacyclooctadecane backbone was replaced with derivatives containing sulfur in the 1,4- or the 1,4,10,13-positions to yield the novel chelators HSmacropa (NOS) and HSmacropa (NOS), respectively. Trends on the Pb- and Bi-complex stability constants, coordination chemistry, radiolabeling, and kinetic inertness were assessed via potentiometric titrations, UV-vis spectroscopy, NMR spectroscopy, X-ray crystallography and density functional theory (DFT) calculations.

Capturing Mercury-197m/g for Auger Electron Therapy and Cancer Theranostic with Sulfur-Containing Cyclen-Based Macrocycles.

The interest in mercury radioisotopes, Hg ( = 23.8 h) and Hg ( = 64.14 h), has recently been reignited by the dual diagnostic and therapeutic nature of their nuclear decays.

Exploration of commercial cyclen-based chelators for mercury-197 m/g incorporation into theranostic radiopharmaceuticals.

A comprehensive investigation of the Hg coordination chemistry and Hg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, -SCN-Bn-DOTA and -SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the Hg theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%-6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10 M). In contrast, -SCN-Bn-TCMC and -SCN-Bn-DOTA demonstrated significantly higher Hg radiochemical yields (100% ± 0.

Tuning the Softness of the Pendant Arms and the Polyazamacrocyclic Backbone to Chelate the Pb/Pb Theranostic Pair.

A series of macrocyclic ligands were considered for the chelation of Pb: 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetrazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetrazacyclotetradecane (TE4S). The equilibrium, the acid-mediated dissociation kinetics, and the structural properties of the Pb complexes formed by these chelators were examined by UV-Visible and nuclear magnetic resonance (NMR) spectroscopies, combined with potentiometry and density functional theory (DFT) calculations. The obtained results indicated that DO4S, DO3S, DO3SAm, and DO2A2S were able to efficiently chelate Pb and that the most suitable macrocyclic scaffold for Pb is 1,4,7,10-tetrazacyclododecane.

Production and radiochemistry of antimony-120m: Efforts toward Auger electron therapy with Sb.

Targeted Meitner-Auger Therapy (TMAT) has potential for personalized treatment thanks to its subcellular dosimetric selectivity, which is distinct from the dosimetry of β and α particle emission based Targeted Radionuclide Therapy (TRT). To date, most clinical and preclinical TMAT studies have used commercially available radionuclides. These studies showed promising results despite using radionuclides with theoretically suboptimal photon to electron ratios, decay kinetics, and electron emission spectra.

Selective Chelation of the Exotic Meitner-Auger Emitter Mercury-197 m/g with Sulfur-Rich Macrocyclic Ligands: Towards the Future of Theranostic Radiopharmaceuticals.

Mercury-197 m/g are a promising pair of radioactive isomers for incorporation into a theranostic as they can be used as a diagnostic agent using SPECT imaging and a therapeutic via Meitner-Auger electron emissions. However, the current absence of ligands able to stably coordinate Hg to a tumour-targeting vector precludes their use in vivo. To address this, we report herein a series of sulfur-rich chelators capable of incorporating Hg into a radiopharmaceutical.

Determination of distribution coefficients of mercury and gold on selected extraction chromatographic resins - towards an improved separation method of mercury-197 from proton-irradiated gold targets.

Radioisotope mercury-197g (Hg, half-life: 64.14 h) along with its metastable isomer (Hg, half-life: 23.8 h) are potential candidates for targeted Meitner-Auger electron therapy due to their suitable decay properties.

Meitner-Auger Electron Emitters for Targeted Radionuclide Therapy: Mercury-197m/g and Antimony-119.

Targeted Radionuclide Therapies (TRTs) based on Auger emitting radionuclides have the potential to deliver extremely selective therapeutic payloads on the cellular level. However, to fully exploit this potential, suitable radionuclides need to be applied in combination with appropriate delivery systems. In this review, we summarize the state-of-the-art production, purification, chelation and applications of two promising candidates for Targeted Auger Therapy, namely antimony- 119 (Sb) and mercury-197 (Hg).

Structure, Anion, and Solvent Effects on Cation Response in ESI-MS.

The abundance of an ion in an electrospray ionization mass spectrum is dependent on many factors beyond just solution concentration. Even in cases where the analytes of interest are permanently charged (under study here are ammonium and phosphonium ions) and do not rely on protonation or other chemical processes to acquire the necessary charge, factors such as cation structure, molecular weight, solvent, and the identity of the anion can affect results. Screening of a variety of combinations of cations, anions, and solvents provided insight into some of the more important factors.