title: A carborane-derivative "click" reaction under heterogeneous conditions for the synthesis of a promising lipophilic MRI/GdBNCT agent.
abstract: In this study, the Huisgen reaction has been used to functionalise a carborane cage with a lipophilic moiety and a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron-capture therapy (BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole units has been accomplished under both heterogeneous conditions, by the use of a Cu-supported ionic-liquid catalyst, and homogeneous conditions. The ability of the Gd complex of the synthesised ligand to form stable adducts with low-density lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour melanoma cells incubated in the presence of a Gd-complex/LDL imaging probe. It has been concluded that the high amount of intracellular boron necessary to perform BNCT can be reached even in the presence of a relatively low-boron-containing LDL concentration.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Torino, Via Pietro Giuria, 7, 10125 Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toppino
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bova
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti Crich
authors.forename: Diego
authors.initials: D
authors.lastname: Alberti
authors.forename: Eliano
authors.initials: E
authors.lastname: Diana
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barge
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Paolo
authors.initials: P
authors.lastname: Venturello
authors.forename: Annamaria
authors.initials: A
authors.lastname: Deagostino
mesh_terms: D000818:Animals; D001692:Biological Transport; D001880:Boranes / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D005682:Gadolinium / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008077:Lipoproteins, LDL / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008546:Melanoma, Experimental / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D051379:Mice
chemical_list: D001880:Boranes; D008077:Lipoproteins, LDL; D003300:Copper; D005682:Gadolinium