Abou, Diane S. published the artcileTowards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand, Recommanded Product: 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid, the publication is Chemical Science (2021), 12(10), 3733-3742, database is CAplus and MEDLINE.
Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [223Ra]RaCl2 is the only clin. approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [223Ra]Ra2+ localizes. To specifically direct [223Ra]Ra2+ to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary. Although previous efforts to stably chelate [223Ra]Ra2+ for this purpose have had limited success, here we report a biol. stable radiocomplex with the 18-membered macrocyclic chelator macropa. Quant. labeling of macropa with [223Ra]Ra2+ was accomplished within 5 min at room temperature with a radiolabeling efficiency of >95%, representing a significant advancement over conventional chelators such as DOTA and EDTA, which were unable to completely complex [223Ra]Ra2+ under these conditions. [223Ra][Ra(macropa)] was highly stable in human serum and exhibited dramatically reduced bone and spleen uptake in mice in comparison to bone-targeted [223Ra]RaCl2, signifying that [223Ra][Ra(macropa)] remains intact in vivo. Upon conjugation of macropa to a single amino acid β-alanine as well as to the prostate-specific membrane antigen-targeting peptide DUPA, both constructs retained high affinity for 223Ra, complexing >95% of Ra2+ in solution Furthermore, [223Ra][Ra(macropa-β-alanine)] was rapidly cleared from mice and showed low 223Ra bone absorption, indicating that this conjugate is stable under biol. conditions. Unexpectedly, this stability was lost upon conjugation of macropa to DUPA, which suggests a role of targeting vectors in complex stability in vivo for this system. Nonetheless, our successful demonstration of efficient radiolabeling of the β-alanine conjugate with 223Ra and its subsequent stability in vivo establishes for the first time the possibility of delivering [223Ra]Ra2+ to metastases outside of the bone using functionalized chelators, marking a significant expansion of the therapeutic utility of this radiometal in the clinic.
Chemical Science published new progress about 1128304-86-8. 1128304-86-8 belongs to pyridine-derivatives, auxiliary class Pyridines, name is 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid, and the molecular formula is C26H36N4O8, Recommanded Product: 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem