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BioMed Research International
Volume 2013 (2013), Article ID 835859, 12 pages
http://dx.doi.org/10.1155/2013/835859
Research Article

Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
2Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA

Received 14 April 2013; Accepted 17 July 2013

Academic Editor: Tapas Das

Copyright © 2013 Nedim C. M. Gulaldi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as , where and represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant . Also significant was the correlation between the retention parameter derived from the tissue activity curve ( ) and the retention parameter derived from the impulse response function ( ). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding.