Sökning: WFRF:(Hosseini A) >
Synthesis, Biodistr...
Synthesis, Biodistribution, and Radiation Dosimetry of a Novel mGluR5 Radioligand : F-18-AZD9272
-
- Nag, Sangram (författare)
- Karolinska Institutet
-
- Varnäs, Katarina (författare)
- Karolinska Institutet
-
- Arakawa, Ryosuke (författare)
- Karolinska Institutet
-
visa fler...
-
- Jahan, Mahabuba (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
-
- Schou, Magnus (författare)
- Karolinska Institutet
-
- Farde, Lars (författare)
- Karolinska Institutet
-
- Halldin, Christer (författare)
- Karolinska Institutet
-
visa färre...
-
(creator_code:org_t)
- 2020-03-13
- 2020
- Engelska.
-
Ingår i: ACS Chemical Neuroscience. - : AMER CHEMICAL SOC. - 1948-7193. ; 11:7, s. 1048-1057
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://pubs.acs.org...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- The metabotropic glutamate receptor subtype mGluR5 has been proposed as a potential drug target for CNS disorders such as anxiety, depression, Parkinson's disease, and epilepsy. The AstraZeneca compound AZD9272 has previously been labeled with carbon-11 and used as a PET radioligand for mGluR5 receptor binding. The molecular structure of AZD9272 allows one to label the molecule with fluorine-18 without altering the structure. The aim of this study was to develop a fluorine-18 analogue of AZD9272 and to examine its binding distribution in the nonhuman primate brain in vivo as well as to obtain whole body radiation dosimetry. F-18-AZD9272 was successfully synthesized from a nitro precursor. The radioligand was stable, with a radiochemical purity of >99% at 2 h after formulation in a sterile phosphate buffered solution (pH = 7.4). After injection of F-18-AZD9272 in two cynomolgus monkeys, the maximum whole brain radioactivity concentration was 4.9-6.7% of the injected dose (n = 2) and PET images showed a pattern of regional radioactivity consistent with that previously obtained for C-11-AZD9272. The percentage of parent radioligand in plasma was 59 and 64% (n = 2) at 120 min after injection of F-18-AZD9272, consistent with high metabolic stability. Two whole body PET scans were performed in nonhuman primates for a total of 231 min after injection of F-18-AZD9272. Highest uptakes were seen in liver and small intestine, followed by brain and kidney. The estimated effective dose was around 0.017 mSv/MBq. F-18-AZD9272 shows suitable properties as a PET radioligand for in vivo imaging of binding in the primate brain. F-18-labeled AZD9272 offers advantages over C-11-AZD9272 in terms of higher image resolution, combined with a longer half-life. Moreover, based on the distribution and the estimated radiation burden, imaging of F-18-AZD9272 could be used as an improved tool for quantitative assessment and characterization of AZD9272 binding sites in the human brain by using PET.
Ämnesord
- NATURVETENSKAP -- Kemi -- Annan kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- PET
- mGluR5 radioligands
- NHP
- fluorine-18
- kinetics
- dosimetry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas