Biological evaluation of two iodine-123-labeled D-glucose acetals prepared as glucose transporter radioligands.
Two iodinated acetals of D-glucose, 4,6-(R)-O-(2'-iodoethylidene)-alpha, beta-D-glucose (1) and 4,6-(R)-O-(4'-iodobenzylidene)-alpha, beta-D-glucose (2), were prepared and their potential as suitable SPECT radioligands for imaging of glucose transporters was studied. Both are analogs of acetal D-glucose derivatives, which are known to bind to the exofacial sites of the glucose transport protein (GluT). To assess whether iodinated acetals 1 and 2 interacted with the glucose transporter, they were tested in vitro in human erythrocytes (GluT1) and neonatal rat cardiomyocytes (GluT4). The results indicated that 1 and 2 had a very low affinity for the glucose transporter and probably accumulated in cells. Study of their tissue distribution was carried out in the mouse in vivo: Both compounds showed fast tissue clearance with preferential renal elimination. It is concluded that iodinated acetals of D-glucose 1 and 2 are not suitable for GluT targeting in vivo.
Brunet-Desruet
M D
MD
Laboratoire D'Etude des Radiopharmaceutiques, ESA CNRS 5077, Faculté de Médecine et de Pharmacie, Université de Grenoble, La Tronche, France.
Ghezzi
C
C
Morin
C
C
Comet
M
M
Fagret
D
D
D000080:Acetals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
C115364:4,6-O-(2'-iodoethylidene)glucose; C115363:4,6-O-(4'-iodoethylidene)glucose; D000080:Acetals; D007457:Iodine Radioisotopes; D008024:Ligands; D009004:Monosaccharide Transport Proteins; D019275:Radiopharmaceuticals; D005947:Glucose