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

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...

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Main Authors:	Gulaldi, Nedim C. M., Xia, Jinsong, Feng, Tao, Hong, Kelvin, Mathews, William B., Ruben, Dawn, Kamel, Ihab R., Tsui, Benjamin M. W., Szabo, Zsolt
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780470/

id	pubmed-3780470
recordtype	oai_dc
spelling	pubmed-37804702013-09-30 Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173 Gulaldi, Nedim C. M. Xia, Jinsong Feng, Tao Hong, Kelvin Mathews, William B. Ruben, Dawn Kamel, Ihab R. Tsui, Benjamin M. W. Szabo, Zsolt Research Article 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 DVR = DVS/DVNS, where DVS and DVNS 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 (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Y ret) and the retention parameter derived from the impulse response function (f ret). 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. Hindawi Publishing Corporation 2013 2013-09-08 /pmc/articles/PMC3780470/ /pubmed/24083243 http://dx.doi.org/10.1155/2013/835859 Text en Copyright © 2013 Nedim C. M. Gulaldi et al. https://creativecommons.org/licenses/by/3.0/ 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gulaldi, Nedim C. M. Xia, Jinsong Feng, Tao Hong, Kelvin Mathews, William B. Ruben, Dawn Kamel, Ihab R. Tsui, Benjamin M. W. Szabo, Zsolt
spellingShingle	Gulaldi, Nedim C. M. Xia, Jinsong Feng, Tao Hong, Kelvin Mathews, William B. Ruben, Dawn Kamel, Ihab R. Tsui, Benjamin M. W. Szabo, Zsolt Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
author_facet	Gulaldi, Nedim C. M. Xia, Jinsong Feng, Tao Hong, Kelvin Mathews, William B. Ruben, Dawn Kamel, Ihab R. Tsui, Benjamin M. W. Szabo, Zsolt
author_sort	Gulaldi, Nedim C. M.
title	Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
title_short	Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
title_full	Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
title_fullStr	Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
title_full_unstemmed	Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173
title_sort	modeling of the renal kinetics of the at1 receptor specific pet radioligand [11c]kr31173
description	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 DVR = DVS/DVNS, where DVS and DVNS 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 (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Y ret) and the retention parameter derived from the impulse response function (f ret). 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.
publisher	Hindawi Publishing Corporation
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780470/
_version_	1612013483634720768

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

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