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

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 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.

Decreased renal AT1 receptor binding in rats after subtotal nephrectomy: PET study with [18F]FPyKYNE-losartan

“…Previous PET studies have explored in vivo renal AT 1 R alterations induced by dietary sodium changes in rats [ 30 ] and in a porcine model of renal ischemia [ 31 ] but not in the hypertensive Nx rat model of CKD. The removal of one kidney and two thirds of the other in the 5/6 Nx rat model of CKD induces a substantial reduction in the number of functioning nephrons [ 1 , 2 ].…”

Total-Body Quantitative Parametric Imaging of Early Kinetics of 18F-FDG

“…Compared with the volume-of-interest (VOI) based kinetic analysis (6,7), parametric imaging enables the acquisition of voxel-level dynamics of the tracer uptake by applying kinetic modeling for each individual voxel (8,9). Conventional graphical methods including Logan analysis (10) and Patlak analysis (11) have been utilized for parametric imaging because of their linear properties and simplicity in acquisition protocols.…”

Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin–Angiotensin System

“…21−26 By applying [ 11 C]KR31173 (Figure 1), it was possible to establish first correlations between arterial and kidney blood input and radioligand uptake in pigs, which makes it a candidate for quantitative evaluation of RAS functions in this organ. 27,28 Recently, the first-in-human study has also been approved and performed, which showed good clinical safety along with detectable and specific myocardial retention. 29 However, it should be pointed out that even though [ 11 C]KR31173 has the above-mentioned properties, the clinical application might be limited due to the general drawbacks of 11 C-labeled tracers as mentioned above.…”