First D1-like receptor PET imaging of the rat and primate kidney: implications for human disease monitoring.

First D1-like receptor PET imaging of the rat and primate kidney: implications for human disease monitoring.
Am J Physiol Renal Physiol. 2014 May 7;
Authors: Granda ML, Schroeder FA, Borra RH, Schauer N, Aisaborhale E, Guimaraes AR, Hooker JM
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 (RAAS). 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 (PET) radioligand for D1-like receptors. In addition we show a D1-like binding potential response to angiotensin II blockade in rat 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 probing human central nervous system 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.
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Source: Am J Physiol Renal P... - May 7, 2014 Category: Urology & Nephrology Authors: Granda ML, Schroeder FA, Borra RH, Schauer N, Aisaborhale E, Guimaraes AR, Hooker JM Tags: Am J Physiol Renal Physiol Source Type: research