PMID- 24083243
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20211021
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2013
DP  - 2013
TI  - Modeling of the renal kinetics of the AT1 receptor specific PET radioligand 
      [11C]KR31173.
PG  - 835859
LID - 10.1155/2013/835859 [doi]
LID - 835859
AB  - PURPOSE: The radioligand [(11)C]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 
      [(11)C]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 = DV(S)/DV(NS), where DV(S) and DV(NS) 
      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.
FAU - Gulaldi, Nedim C M
AU  - Gulaldi NC
AD  - Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins 
      Medical Institutions, Baltimore, MD 21287, USA.
FAU - Xia, Jinsong
AU  - Xia J
FAU - Feng, Tao
AU  - Feng T
FAU - Hong, Kelvin
AU  - Hong K
FAU - Mathews, William B
AU  - Mathews WB
FAU - Ruben, Dawn
AU  - Ruben D
FAU - Kamel, Ihab R
AU  - Kamel IR
FAU - Tsui, Benjamin M W
AU  - Tsui BM
FAU - Szabo, Zsolt
AU  - Szabo Z
LA  - eng
GR  - R01 DK050183/DK/NIDDK NIH HHS/United States
GR  - S10 RR022528/RR/NCRR NIH HHS/United States
GR  - S10 RR022528-01A1/RR/NCRR NIH HHS/United States
GR  - R01DK050183/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130908
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 
      (2-butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-((2'-(1H-tetrazol-5-yl)bipohenyl-4-yl)methyl)-3H-imidazo(4,5-b)pyridine)
RN  - 0 (Imidazoles)
RN  - 0 (Ligands)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tetrazoles)
SB  - IM
MH  - Angiography
MH  - Animals
MH  - Autoradiography
MH  - Blood Cell Count
MH  - Hemodynamics/drug effects
MH  - Imidazoles/chemistry/*pharmacokinetics/pharmacology
MH  - Kidney/*diagnostic imaging/drug effects/metabolism
MH  - Kinetics
MH  - Ligands
MH  - *Models, Biological
MH  - *Positron-Emission Tomography
MH  - Radiopharmaceuticals/chemistry/*pharmacokinetics/pharmacology
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Sus scrofa
MH  - Tetrazoles/chemistry/*pharmacokinetics/pharmacology
PMC - PMC3780470
EDAT- 2013/10/02 06:00
MHDA- 2014/04/16 06:00
PMCR- 2013/09/08
CRDT- 2013/10/02 06:00
PHST- 2013/04/14 00:00 [received]
PHST- 2013/07/17 00:00 [accepted]
PHST- 2013/10/02 06:00 [entrez]
PHST- 2013/10/02 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2013/09/08 00:00 [pmc-release]
AID - 10.1155/2013/835859 [doi]
PST - ppublish
SO  - Biomed Res Int. 2013;2013:835859. doi: 10.1155/2013/835859. Epub 2013 Sep 8.