Development of 123I-labelled NNC 13-8241 as a radioligand for SPECT visualization of benzodiazepine receptor binding.
[125I]- and [123I]NNC 13-8241 were prepared from the trimethyltin precursor and radioactive iodide using the chloramine-T method. The total radiochemical yields of [125I]- and [123I]NNC 13-8241 were 60-70% and 40-50% respectively, with radiochemical purity higher than 98%. In binding studies with [125I]NNC 13-8241 in rats in vitro and in vivo a high uptake of radioactivity was demonstrated in brain regions known to have a high density of benzodiazepine (BZ) receptors such as the occipital and frontal cortex. SPECT examination with [123I]NNC 13-8241 in a Cynomolgus monkey demonstrated a high uptake of radioactivity in the occipital and frontal cortex. After displacement with flumazenil radioactivity in these brain regions was reduced to the level of a central region including the pons. Four hours after injection about 80% of the radioactivity in monkey plasma represented unchanged radioligand. This low degree of metabolism indicates that NNC 13-8241 is metabolically more stable than the radioligands hitherto developed for imaging of BZ-receptors in the primate brain.
Foged
C
C
Karolinska Institute, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Halldin
C
C
Hiltunen
J
J
Braestrup
C
C
Thomsen
C
C
Hansen
H C
HC
Suhara
T
T
Pauli
S
S
Swahn
C G
CG
Karlsson
P
P
Larsson
S
S
Farde
L
L
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism* / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D007457:Iodine Radioisotopes; C100658:NNC 13-8241; D011963:Receptors, GABA-A; D001569:Benzodiazepines