496-P: A New Method to Image Sweet Taste Receptors in the Pathogenesis of Diabetic Nephropathy: Detection of 18F Lactisole with PET/CT

Abstract

Previous studies showed that the expression of sweet taste receptors (STRs) was obviously downregulated in the pathogenesis of diabetic nephropathy (DN), suggesting that STRs may act as new therapeutic targets of DN. However, STRs are weakly expressed in kidneys, it is necessary to find a non-invasive method for detection of STRs distribution in the whole body and kidney. Lactisole, a broad-acting sweet antagonist, is commercially available and may be useful to assess the function and physiological role of the STRs. Whether the detection of isotope 18 F labeled lactisole ( 18 F-lactisole) with PET/CT can be used as a probe for imaging STRs expression differences is unclear. In this study, DN mouse model was induced by streptozotocin (STZ) in vivo, mouse glomerular mesangial cells (GMCs) and human proximal tubular cells (HK-2) were stimulated by high glucose in vitro, exogenous lactisole was used as an intervention reagent, 18 F-lactisole was used as probe agent to evaluate the expression and distribution of STRs in the pathogenesis of DN. Our results showed that both the expression and distribution of STRs in mice were clearly imaged by PET/CT via intravenous injection of 18 F-lactisole, 18 F-lactisole signal in renal tissue was attenuated under the condition of diabetes, this trend persisted 2 hours after furosemide injection. Furthermore, exogenous lactisole significantly mitigated the effect of high glucose on STRs in vitro and vivo, which were detected by PET/CT or radioactive dosimeter via 18 F-lactisole. These combined results support the hypothesis that detection of 18 F-lactisole with PET/CT can be used as a new probe to image STRs and distinguish its expression level, suggesting a new method for non-invasive diagnosis of DN. Disclosure L. Zhou: None. W. Huang: None. N. Liu: None. X.M. Ma: None. M. Guo: None. Q. Chen: None. C. Gao: None. Y. Xu: None.