Search: onr:"swepub:oai:DiVA.org:uu-185287" >
Synthesis and precl...
Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil.
-
- Verbeek, Joost (author)
- VU University Medical Center Amsterdam
-
- Syvänen, Stina (author)
- Leiden University
-
Schuit, Robert C (author)
-
show more...
-
- Eriksson, Jonas (author)
- VU University Medical Center Amsterdam
-
de Lange, Elizabeth C (author)
-
Windhorst, Albert D (author)
-
Luurtsema, Gert (author)
-
Lammertsma, Adriaan A (author)
-
show less...
-
(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- English.
-
In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 530-9
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- OBJECTIVES: (R)-[(11)C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood-brain barrier in man. A disadvantage of (R)-[(11)C]verapamil is the fact that its main metabolite, [(11)C]D617, also enters the brain. For quantitative analysis of (R)-[(11)C]verapamil data, it has been assumed that the cerebral kinetics of (R)-[(11)C]verapamil and [(11)C]D617 are the same. The aim of the present study was to investigate whether the cerebral kinetics of (R)-[(11)C]verapamil and [(11)C]D617 are indeed similar and, if so, whether [(11)C]D617 itself could serve as an alternative PET tracer for P-gp.METHODS: [(11)C]D617 was synthesized and its ex vivo biodistribution was investigated in male rats at four time points following intravenous administration of [(11)C]D617 (50 MBq) without (n=4) or with (n=4) pretreatment with the P-gp inhibitor tariquidar (15 mg·kg(-1), intraperitoneally). Brain distribution was further assessed using consecutive PET scans (n=8) before and after pretreatment with tariquidar (15 mg·kg(-1), intravenously), as well as metabolite analysis (n=4).RESULTS: The precursor for the radiosynthesis of [(11)C]D617, 5-amino-2-(3,4-dimethoxy-phenyl)-2-isopropyl-pentanitrile (desmethyl D617), was synthesized in 41% overall yield. [(11)C]D617 was synthesized in 58%-77% decay-corrected yield with a radiochemical purity of ≥99%. The homogeneously distributed cerebral volume of distribution (V(T)) of [(11)C]D617 was 1.1, and this increased 2.4-fold after tariquidar pretreatment.CONCLUSION: V(T) of [(11)C]D617 was comparable to that of (R)-[(11)C]verapamil, but its increase after tariquidar pretreatment was substantially lower. Hence, (R)-[(11)C]verapamil and [(11)C]D617 do not show similar brain kinetics after inhibition of P-gp with tariquidar.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database