Analysis of [11C]methyl-candesartan kinetics in the rat kidney for the assessment of angiotensin II type 1 receptor density in vivo with PET.
BACKGROUND
Angiotensin II type 1 (AT(1)) receptors play a key role in the regulation of renal and cardiovascular functions and have been implicated in the pathogenesis of many diseases. The aim of this study was to assess binding of the novel radioligand [(11)C]methyl-candesartan to AT(1) receptors in the rat kidney in vivo with PET.


METHODS
Dynamic PET images were acquired for 60 min at baseline, with coinjection of candesartan (5 mg/kg), and after injection of PD123,319 (5 mg/kg). Volumes of distribution (R(C)∙V(T)) were estimated with a two-compartment model, by Logan analysis, and by taking the tissue-to-plasma activity ratio at 50-60 min post-injection.


RESULTS
The two-compartment model did not describe the kinetics at baseline adequately and the baseline scans were too short to obtain accurate estimates of R(C)∙V(T) with the Logan approach. Based on the tissue-to-plasma ratios, roughly one-third of V(T) at baseline could be attributed to AT(1) receptor binding. There were no indications of AT(2) receptor binding in the rat kidney.


CONCLUSIONS
It may be possible to detect changes in AT(1) receptor density in the rat kidney in vivo with [(11)C]methyl-candesartan and PET. Imaging AT(1) receptors with PET may provide valuable information on the role of these receptors in the pathogenesis of diseases such as hypertension, diabetic nephropathy, ventricular remodeling, and heart failure.
Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7.
Mireille
M
Lortie
Jean N
JN
DaSilva
Sheryn A
SA
Kirkpatrick
Tayebeh
T
Hadizad
Basma A
BA
Ismail
Rob S B
RS
Beanlands
Robert A
RA
deKemp
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000097:blood / Q000378:metabolism*; D001713:Biphenyl Compounds; D002250:Carbon Radioisotopes; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015203:Reproducibility of Results; D013777:Tetrazoles / Q000097:blood / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002250:Carbon Radioisotopes; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C582420:methyl-2-ethoxy-1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-benzimidazole-7-carboxylate; C073402:PD 123319; C081643:candesartan