Radiosynthesis and biodistribution of 123I-labeled antagonists of the histamine H3 receptor as potential SPECT ligands.
We have synthesized three 123I-labeled histamine H3 receptor ligands, i.e., [123I]GR 190028, [123I]FUB 271, and [123I]iodoproxyfan, in moderate to good radiochemical yields via a Cu+-assisted I-for-123I exchange method. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [123I]iodoproxyfan, brain uptake was high enough for a pilot single photon emission computed tomography (SPECT) study in the rabbit. However, for this compound, the cerebral uptake could not be blocked by a pretreatment with [R]-alpha-methylhistamine, a selective, high-affinity histamine H3 receptor agonist, both in the SPECT study in the rabbit and in the biodistribution study in the rat. Apparently, [123I]iodoproxyfan is binding to a non-H3 receptor binding site. None of the three investigated compounds is suitable for use as a SPECT ligand for the H3 receptor in the brain.
Windhorst
A D
AD
Radionuclide Center, Vrije Universiteit, Amsterdam, The Netherlands. bwindhorst@rnc.vu.nl
Timmerman
H
H
Klok
R P
RP
Custers
F G
FG
Menge
W M
WM
Leurs
R
R
Stark
H
H
Schunack
W
W
Gielen
E G
EG
van Kroonenburgh
M J
MJ
Herscheid
J D
JD
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007462:Iodobenzenes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008297:Male; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000032:analysis*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C402166:FUB 271; C402165:GR 190028; D006633:Histamine Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D010069:Oxadiazoles; D018100:Receptors, Histamine H3; C090115:iodoproxyfan