Inorganic radiopharmaceutical chemistry of oxine

8-Hydroxyquinoline (8-HQ, oxine) is a small, monoprotic, bicyclic aromatic compound and its relative donor group orientation imparts impressive bidentate metal chelating abilities that have been exploited in a vast array of applications over decades. 8-HQ and its derivatives have been explored in medicinal applications including anti-neurodegeneration, anticancer properties, and antimicrobial activities. One long established use of 8-HQ in medicinal inorganic chemistry is the coordination of radioactive isotopes of metal ions in nuclear medicine. The metal-oxine complex with the single photon emission computed tomography (SPECT) imaging isotope [In-111]In3+ was developed in the 1970s and 1980s to radiolabel leukocytes for inflammation and infection imaging. The [In-111][In(oxine)(3)] complex functions as an ionophore: a moderately stable lipophilic complex to enter cells; however, inside the cell environment [In-111]In3+ undergoes exchange and remains localized. As new developments have progressed towards radiopharmaceuticals capable of both imaging and therapy (theranostics), 8-HQ has been re-explored in recent years to investigate its potential to chelate larger radiometal ions with longer half-lives and different indications. Further, metal-oxine complexes have been used to study liposomes and other nanomaterials by tracking these nanomedicines in vivo. Expanding 8-HQ to multidentate ligands for highly thermodynamically stable and kinetically inert complexes has increased the possibilities of this small molecule in nuclear medicine. This article outlines the historic use of metal-oxine complexes in inorganic radiopharmaceutical chemistry, with a focus on recent advances highlighting the possibilities of developing higher denticity, targeted bifunctional chelators with 8-HQ.

Automated summary

8-Hydroxyquinoline is a versatile compound with impressive metal chelating abilities, utilized in various fields such as medicine, nuclear medicine, and nanotechnology. Recent research has focused on its potential to chelate larger radiometal ions with longer half-lives and different indications.