Radioiodinated benzodiazepines: agents for mapping glial tumors.
Two isomeric iodinated analogues of the peripheral benzodiazepine binding site (PBS) ligand Ro5-4864 have been synthesized and labeled in high specific activity with iodine-125. Competitive binding assays conducted with the unlabeled analogues indicate high affinity for PBS. Tissue biodistribution studies in rats with these 125I-labeled ligands indicate high uptake of radioactivity in the adrenals, heart, and kidney--tissues known to have high concentrations of PBS. Preadministration of the potent PBS antagonist PK 11195 blocked in vivo uptake in adrenal tissue by over 75%, but to a lesser degree in other normal tissues. In vivo binding autoradiography in brain conducted in C6 glioma bearing rats showed dense, PBS-mediated accumulation of radioactivity in the tumor. Ligand 6 labeled with 123I may have potential for scintigraphic localization of intracranial glioma.
Van Dort
M E
ME
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Ciliax
B J
BJ
Gildersleeve
D L
DL
Sherman
P S
PS
Rosenspire
K C
KC
Young
A B
AB
Junck
L
L
Wieland
D M
DM
D000818:Animals; D001345:Autoradiography; D001570:Benzodiazepinones; D001667:Binding, Competitive; D005910:Glioma / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007546:Isoquinolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000032:analysis*
D001570:Benzodiazepinones; D007457:Iodine Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C037850:PK 11195