Despite its prevalence in the environment, the chemistry of the Ti4+ ion has long been relegated to organic solutions or hydrolyzed TiO2 polymorphs. A knowledge gap in stabilizing molecular Ti4+ species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water‐compatible metal–organic frameworks (MOFs), and aqueous‐phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti4+ in aqueous solution, as well as computational and structural analyses of key compounds. In addition, the hexadentate analogues of catechol (benzene‐1,2‐diol) and deferiprone (3‐hydroxy‐1,2‐dimethyl‐4(1H)‐pyridone), TREN‐CAM and THPMe respectively, were assessed for chelation of the 45Ti isotope (t1/2=3.08 h, β+=85 %, Eβ+=439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit‐formulation, and [45Ti]Ti‐TREN‐CAM was found to have remarkable stability in vivo.

The radioactive isotopes scandium-44/47 and lutetium-177 are gaining relevance for radioimaging and radiotherapy, resulting in a surge of studies on their coordination chemistry and subsequent applications. Although the trivalent ions of these elements are considered close homologues, dissimilar chemical behavior is observed when they are complexed by large ligand architectures due to discrepancies between Lu(III) and Sc(III) ions with respect to size, chemical hardness, and Lewis acidity. Here, we demonstrate that Lu and Sc complexes of 1,4bis(methoxycarbonyl)-7-[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane (H 3 mpatcn) and its corresponding bioconjugate picaga-DUPA can be employed to promote analogous structural features and, subsequently, biological properties for coordination complexes of these ions. The close homology was evidenced using potentiometric methods, computational modeling, variable temperature mass spectrometry, and pair distribution function analysis of X-ray scattering data. Radiochemical labeling, in vitro stability, and biodistribution studies with Sc-47 and Lu-177 indicate that the 7coordinate ligand environment of the bifunctional picaga ligand is compatible with biological applications and the future investigation of β-emitting, picaga-chelated Sc and Lu isotopes for radiotherapy. Special Issue: State-of-the-Art of Radiometal-based Bioconjugates for Molecular Imaging and Radiotherapy

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Fluorine-18 remains the most widely clinically utilized radionuclide globally for positron emission tomography (PET). The emergence of therapeutic isotopes for the management of disease has produced a pronounced interest in matched, theranostic isotope pairs that can be employed in tandem for the diagnosis and stratification of patients for subsequent radiotherapy. 18 F, however, does not have a suitable therapeutic isotopologue. Here, we demonstrate that the formation of [ 18 F][ScÀ F] ternary complexes is feasible under mild, aqueous conditions, producing chemically robust radiopharmaceuticals in high radiochemical yield and specific activity. A corresponding in vivo study with a cancer-targeting [ 18 F][ScÀ F] tracer indicates excellent in vivo stability and produces exquisite PET image quality, rendering the 18 F/ 47 Sc isotope pair an unusual, yet chemically matched theranostic pair with excellent potential for clinical translation.

Despite its prevalence in the environment, the chemistry of the Ti 4 + ion has long been relegated to organic solutions or hydrolyzed TiO 2 polymorphs. A knowledge gap in stabilizing molecular Ti 4 + species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water-compatible metal-organic frameworks (MOFs), and aqueous-phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti 4 + in aqueous solution, as well as computational and structural analyses of key compounds. In addition, the hexadentate analogues of catechol (benzene-1,2-diol) and deferiprone (3-hydroxy-1,2-dimethyl-4(1H)-pyridone), TREN-CAM and THP Me respectively, were assessed for chelation of the 45 Ti isotope (t 1/2 = 3.08 h, β + = 85 %, E β + = 439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit-formulation, and [ 45 Ti]Ti-TREN-CAM was found to have remarkable stability in vivo.