title: First D1-like receptor PET imaging of the rat and primate kidney: implications for human disease monitoring.
abstract: The intrarenal dopamine system is important for signaling and natriuresis, and significant dysfunction is associated with hypertension and kidney disease in ex vivo studies. Dopamine receptors also modulate and are modulated by the renin-angiotensin-aldosterone system. Here, we show the first in vivo measurement of D1-like receptors in the renal cortex of Sprague-Dawley rat and Papio anubis baboon using [(11)C]NNC 112, a positron emission tomography radioligand for D1-like receptors. In addition, we show a D1-like binding potential response to angiotensin II blockade in rats using losartan. Demonstration of self-saturable binding in the rat as well as specific and saturable binding in Papio anubis validate the use of [(11)C]NNC 112 in the first in vivo measurement of renal dopamine D1-like receptors. Furthermore, [(11)C]NNC 112 is a radioligand tool already validated for use in probing human central nervous system (CNS) D1-like receptors. Our work demonstrates specific and saturable non-CNS binding in higher animals and the ability to quantify physiological response to drug treatment and provides a clear path to extend use of [(11)C]NNC 112 to study renal dopamine in humans.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Granda
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schroeder
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
authors.forename: Ronald H J
authors.initials: RH
authors.lastname: Borra
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
authors.forename: Nathan
authors.initials: N
authors.lastname: Schauer
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
authors.forename: Ehimen
authors.initials: E
authors.lastname: Aisaborhale
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Guimaraes
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and hooker@nmr.mgh.harvard.edu.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D048530:Papio anubis; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D001552:Benzazepines; D001572:Benzofurans; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; C077123:NNC 112; D004298:Dopamine
keywords: dopamine; hypertension; positron emission tomography; renal PET; renal dopamine