Biological evaluation of two iodine-123-labeled D-glucose acetals prepared as glucose transporter radioligands.

ABSTRACT

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.