UNLABELLED: P-glycoprotein (P-gp) regulates the ability of endogenous and exogenous compounds to cross the blood-brain barrier. We investigated whether PET tracers used clinically for studying brain function are affected by P-gp. METHODS: Modulation of 8 radioligands by P-gp was assayed in mice by evaluating the effect of treatment with cyclosporine A (CsA) on uptake into the brain (assay 1) and the effect of treatment with a cold ligand of the corresponding radioligand on uptake of (11)C-verapamil, a representative radioligand for P-gp (assay 2). Brain-to-blood ratios were also examined as the other index to correct the delivery of radioligands. The radioligands investigated were (11)C-TMSX (adenosine A(2A) receptor), (11)C-MPDX (adenosine A(1) receptor), (11)C-PK11195 (peripheral benzodiazepine receptor), (11)C-flumazenil (central benzodiazepine receptor), (11)C-raclopride (dopamine D(2)-like receptor), (11)C-pyrilamine (histamine H(1) receptor), (11)C-PIB (amyloid plaque), and (11)C-donepezil (acetylcholine esterase). RESULTS: In assay 1, CsA treatment increased both the uptake and the brain-to-blood ratio of (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil among the 8 radioligands. In assay 2, in which 4 cold ligands were examined, cold verapamil slightly increased the brain-to-blood ratio of (11)C-verapamil, but TMSX, MPDX, and MPPF did not increase either parameter. CONCLUSION: Assay 1 was suitable for evaluating the P-gp modulation of radioligands. Among the 8 radioligands investigated, (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil were modulated by P-gp.
UNLABELLED: P-glycoprotein (P-gp) regulates the ability of endogenous and exogenous compounds to cross the blood-brain barrier. We investigated whether PET tracers used clinically for studying brain function are affected by P-gp. METHODS: Modulation of 8 radioligands by P-gp was assayed in mice by evaluating the effect of treatment with cyclosporine A (CsA) on uptake into the brain (assay 1) and the effect of treatment with a cold ligand of the corresponding radioligand on uptake of (11)C-verapamil, a representative radioligand for P-gp (assay 2). Brain-to-blood ratios were also examined as the other index to correct the delivery of radioligands. The radioligands investigated were (11)C-TMSX (adenosine A(2A) receptor), (11)C-MPDX (adenosine A(1) receptor), (11)C-PK11195 (peripheral benzodiazepine receptor), (11)C-flumazenil (central benzodiazepine receptor), (11)C-raclopride (dopamine D(2)-like receptor), (11)C-pyrilamine (histamine H(1) receptor), (11)C-PIB (amyloid plaque), and (11)C-donepezil (acetylcholine esterase). RESULTS: In assay 1, CsA treatment increased both the uptake and the brain-to-blood ratio of (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil among the 8 radioligands. In assay 2, in which 4 cold ligands were examined, cold verapamil slightly increased the brain-to-blood ratio of (11)C-verapamil, but TMSX, MPDX, and MPPF did not increase either parameter. CONCLUSION: Assay 1 was suitable for evaluating the P-gp modulation of radioligands. Among the 8 radioligands investigated, (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil were modulated by P-gp.
Authors: Goran Laćan; Alain Plenevaux; Daniel J Rubins; Baldwin M Way; Caroline Defraiteur; Christian Lemaire; Joel Aerts; André Luxen; Simon R Cherry; William P Melega Journal: Eur J Nucl Med Mol Imaging Date: 2008-07-05 Impact factor: 9.236
Authors: Junfeng Li; Xiang Zhang; Zhanbin Zhang; Prashanth K Padakanti; Hongjun Jin; Jinquan Cui; Aixiao Li; Dexing Zeng; Nigam P Rath; Hubert Flores; Joel S Perlmutter; Stanley M Parsons; Zhude Tu Journal: J Med Chem Date: 2013-07-18 Impact factor: 7.446
Authors: Zhude Tu; Shihong Li; Jinbin Xu; Wenhua Chu; Lynne A Jones; Robert R Luedtke; Robert H Mach Journal: Nucl Med Biol Date: 2011-03-03 Impact factor: 2.408
Authors: P Blanckaert; I Burvenich; S Staelens; S De Bruyne; L Moerman; L Wyffels; F De Vos Journal: Eur J Nucl Med Mol Imaging Date: 2008-11-05 Impact factor: 9.236