The preliminary assessment of renal function of a ¹⁸F labeled hippurate analogue, N-(6-[¹⁸F]Fluoropyridin-3-yl)glycine, using two rat models

Objectives: Positron emission tomography has irreplaceable advantages in localization and quantification of lesions due to its high spatial resolution and high sensitivity. Single-photon emission computed tomography imaging is recognized as a non-invasive method for the assessment of various kidney diseases and the monitoring of renal function in chronic kidney diseases. However, SPECT has some disadvantages such as limited structural information, low image quality and poor quantitative data. The purpose of this study was to evaluate the feasibility of a fluorine-18 labeled hippurate analogue, N-(6-[¹⁸F] fluoropyridine-3-yl) glycine reported in our previous research, as a PET agent for the assessment of renal function using renal ischemia-reperfusion injuryrat modeland type 2 diabetic nephropathyrat model.

Methods: 12 male SD rats were randomly divided into 3 groups. Thefour rats were given sugrose -fat enrich diet only as control group. Rat model of renal ischemia-reperfusion injury were prepared from the block of the two renal pedicles for 50 min with microaneurysm clamps and the remove of the clamps for the restoration of blood flow. Rat model of renal type 2 diabetic nephropathy was prepared from the one dose injection of streptozotocin (30 mg/(kg·BW)), and then the fed continually with high-carbonhydrate-fat feeds until the presence of the glucose tolerance abnormity and renal pathological changes confirmed by pathology. Dynamic micro-PET/CT imaging was performed on healthy rats (control group), rat models of renal ischemia-reperfusion injury (renal ischemia-reperfusion injury group) and type 2 diabetic nephropathy (type 2 diabetic nephropathy group), and the peak time T_max and the excretion time of imaging agents to 1/2 peak time T_1/2max were compared for these three groups.

Results: The kidney time-activity curves of N-(6-[¹⁸F] fluoropyridine-3-yl) glycinefor control group showed that the time to peak activity T_max was 1.35±0.15min, and the time to half-maximal activity T_1/2max was 2.90±0.26min. Forrenal ischemia-reperfusion injury group, T_max and T_1/2max were significantly delayed compared to control group (T_max=1.75±0.10min and T_{1/2 Max} =7.20±0.55min, p<0.05), indicating that renal perfusion and excretion were damaged to a different extent. The T_max of the diabetic nephropathy rat model was also significantly delayed but no obvious imaging agent excretion process was observed (T_max=2.75±0.30min, T_{1/2 Max} over than 60min), indicating that the glomerular function was seriously impaired, which was consistent with the pathological changes of diabetic nephropathy. Conclusion: N-(6-[¹⁸F] fluoropyridine-3-yl) glycine as a renal PET agent has positive effects in the assessment of renal function for rat models of the renal ischemia-reperfusion injury and diabetic nephropathy. It is worth for the further evaluation of feasibility of this probe in other renal dysfunction diseases.

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