title: Long-chain rhenium and technetium glucosamine conjugates.
abstract: A series of five glucosamine-conjugated organometallic complexes of the tricarbonyl cores of technetium-99m and rhenium were made. Glucosamine was derivatized at the C-2 nitrogen with long chain alkyl spacers linked to either pyridyl-tert-nitrogen-phenol tridentate chelates or cyclopentadienyl ligating groups. The metal complexes of the tridentate ligands were formed by refluxing with [Re(CO)(3)(H(2)O)(3)]Br, or with a base and [(99m)Tc(CO)(3)(H(2)O)(3)](+). These ligands were found to be competent chelates in binding the [(99m)Tc(CO)(3)](+) core as radiolabeling yields ranged from 87 to 93% and the resulting complexes are stable to cysteine and histidine challenges for 24 h. The cyclopentadienyl analogues were formed using a double ligand transfer reaction for the rhenium complexes and a single ligand transfer for the technetium-99m complexes. All five rhenium complexes were tested as substrates of hexokinase; two of these complexes were tested as hexokinase inhibitors and they were found to be competent inhibitors, suggesting that they may be able to interact with hexokinase. MTT cytotoxicity studies were performed and the complexes tested were found to be non-toxic to the concentrations tested (100 microM or 1 mM). GLUT-1 mediated cell uptake studies were performed on all five technetium-99m complexes, and their cell entry was found to parallel their lipophilicities, suggesting that cellular uptake is by passive diffusion and is not mediated by GLUT-1.
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
authors.forename: Meryn L
authors.initials: ML
authors.lastname: Bowen
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Roos
authors.forename: Ripen
authors.initials: R
authors.lastname: Misri
authors.forename: Urs
authors.initials: U
authors.lastname: Häfeli
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adam
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
mesh_terms: D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005944:Glucosamine / Q000737:chemistry*; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling; D015609:Organotechnetium Compounds / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*
chemical_list: C511834:99mTc(CO)3(LAN); D056831:Coordination Complexes; D015609:Organotechnetium Compounds; D012211:Rhenium; D006593:Hexokinase; D005944:Glucosamine