In vivo imaging and quantitative analysis of TSPO in rat peripheral tissues using small-animal PET with [18F]FEDAC.
BACKGROUND
The translocator protein (18 kDa) (TSPO) is widely expressed in peripheral tissues, including the heart, lung, and kidney. Our laboratory developed N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[(18)F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ([(18)F]FEDAC) as a TSPO positron emission tomography (PET) ligand. Here, using small-animal PET with [(18)F]FEDAC, we performed TSPO imaging and quantitative analysis of TSPO binding in rat peripheral tissues.


METHODS
The in vivo distribution and kinetics of [(18)F]FEDAC were measured in rat peripheral tissues (heart, lung and kidney). Using the in vivo pseudo-equilibrium method, TSPO binding parameters [TSPO density (B(max)), dissociation constant (K(D))] and receptor occupancy were estimated in these peripheral tissues.


RESULTS
[(18)F]FEDAC was highly distributed in the lung, heart and kidney, and these TSPO-enriched tissues could be clearly visualized. The kinetics of this radioligand in these tissues was rapid, which is suitable for the determination of in vivo TSPO binding parameters and receptor occupancy. The B(max) value of TSPO in the heart, lung, and kidney was 393, 141, and 158 pmol/ml, respectively. The K(D) value of the radioligand in the heart, lung, and kidney was 119, 36 and 123 nM, respectively. By pretreatment with 5 mg/kg Ro 5-4864 (a TSPO ligand), about 90% of binding sites for TSPO in the heart and lung were occupied. In the kidney, the binding sites were completely occupied by 5 mg/kg Ro 5-4864.


CONCLUSIONS
[(18)F]FEDAC is a suitable PET ligand for TSPO imaging and quantitative analysis of TSPO binding in rat peripheral tissues. The utilization of [(18)F]FEDAC-PET and the pseudo-equilibrium method can contribute to the study of the TSPO function and evaluate the in vivo binding parameters and receptor occupancy of TSPO therapeutic compounds.
Yanamoto
Kazuhiko
K
Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Kumata
Katsushi
K
Fujinaga
Masayuki
M
Nengaki
Nobuki
N
Takei
Makoto
M
Wakizaka
Hidekatsu
H
Hosoi
Rie
R
Momosaki
Sotaro
S
Yamasaki
Tomoteru
T
Yui
Joji
J
Kawamura
Kazunori
K
Hatori
Akiko
A
Inoue
Osamu
O
Zhang
Ming-Rong
MR
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging*; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
D001570:Benzodiazepinones; D002352:Carrier Proteins; D003292:Convulsants; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C028513:4'-chlorodiazepam