A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells.
A straightforward synthetic route for a new multifunctional 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivative is described. To demonstrate the versatility of this pro-chelator for the preparation of radiolabeled hybrid compounds containing two different biological targeting moieties, an antitumor agent (e.g., a DNA-intercalating agent) and an estrogen receptor (ER) ligand (e.g., LXXLL-based peptide) were regiospecifically conjugated to the DOTA derivative. The bifunctional probe was radiolabeled with the auger electron emitter indium-111, and the resulting radioconjugate was demonstrated to induce DNA damage in vitro, which, along with the nuclear internalization exhibited in breast cancer cells, might enhance its therapeutic activity. This favorable in vitro performance suggests that these hybrid compounds could be attractive probes for theranostic applications.
['Vultos|Filipe|F|', 'Fernandes|Célia|C|', 'Mendes|Filipa|F|', 'Marques|Fernanda|F|', 'Correia|João D G|JDG|', 'Santos|Isabel|I|', 'Gano|Lurdes|L|0000-0001-7186-2060']
D000818:Animals D000970:Antineoplastic Agents D001372:Aza Compounds D001943:Breast Neoplasms D002470:Cell Survival D002614:Chelating Agents D005260:Female D006573:Heterocyclic Compounds, 1-Ring D006801:Humans D007205:Indium Radioisotopes D007364:Intercalating Agents D008024:Ligands D061986:MCF-7 Cells D051379:Mice D010455:Peptides D011485:Protein Binding D019275:Radiopharmaceuticals D011960:Receptors, Estrogen
cancer indium macrocycles radiochemistry