GFR-Vivo 680 Fluorescent Imaging Agent

An in vivo non-invasive method to determine glomerular filtration rate (GFR). Glomerular filtration rate (GFR) is the gold standard in kidney function assessment and is used to determine progression of kidney disease and drug-induced kidney toxicity. One of the most accepted ways to assess GFR is by measuring the rate of disappearance of labeled inulin from the blood; as inulin is completely filtered at the kidneys’ glomeruli (but neither secreted nor reabsorbed by the tubules), this rate of disappearance is directly proportional to GFR. We have developed a near infrared (NIR) fluorescent-labeled form of inulin (GFR-Vivo™ 680) in a spectral region providing low background and high tissue penetration (ex/em = 670/685 nm) for in vivo application. Fluorescence molecular tomographic (FMT) imaging of the heart was used to detect and quantify blood levels of GFR-Vivo 680 at multiple time points, providing the necessary data to calculate the clearance rates in individual animals. Following an intravenous bolus of NIR-Inulin in SKH-1E mice, FMT® images were acquired at 1, 5, 15, 30, and 45 minutes post-injection. Clearance rates were calculated using a two-compartment curve fitting, yielding average rates of 270 + 6 mL/min in normal mice. GFR-Vivo 680, in combination with FMT heart imaging, provides a non-invasive fluorescent imaging approach to generate consistent GFR measurements in models of kidney disease, dysfunction, and drug toxicity.

GFR-Vivo 680 is a near infrared fluorescent inulin based imaging agent that, in combination with fluorescence tomography heart imaging, enables quantitative assessment of renal Glomerular Filtration Rate, as an indicator of renal toxicity or injury.

WMIC2013 Poster_,The measurement of glomerular filtration rate (GFR) is the,gold standard in kidney function assessment and is used to,determine progression of kidney disease and drug-induced,kidney toxicity. This is often assessed indirectly in,preclinical animal models either by surrogate markers, like,plasma creatinine or blood urea nitrogen. GFR is best,quantified functionally by assessing plasma clearance rates,of labeled inulin or labeled inulin analogs, but to-date this,requires blood sampling - a fairly labor intensive process.,In an effort to eliminate this procedure, we developed a,near infrared (NIR) fluorescent-labeled version of inulin,(GFR-Vivo 680 [GFR680]; ex/em = 670/685 nm) in a,spectral wavelength that offers high tissue penetration and,low background suitable for in vivo imaging.

The measurement of glomerular filtration rate (GFR) is the gold standard in kidney function assessment and is used to determine progression of kidney disease and drug-induced kidney toxicity. GFR has been typically determined in preclinical animal models through measurement of radiolabeled inulin clearance from the circulation, requiring serial bleeding of multiple cohorts of animals. We have developed a near infrared (NIR) fluorescent-labeled form of inulin (GFR-Vivo 680; ex/em = 670/685 nm) in a spectral region providing low background and high tissue penetration for in vivo application. Fluorescence molecular tomographic (FMT) imaging of an intravenous bolus of GFR-Vivo 680 in SKH-1E mice provides 3D quantitative fluorescent images of heart fluorescence over time (1-45 minutes postinjection). GFR was calculated using a two-compartment model (PK Solver 2.0), determining average rates of 240-280 µL/min in normal mice. These results were comparable to kinetic studies in which multiple cohorts of mice receiving GFR-Vivo 680 were assayed ex vivo. In comparison, nephrectomized mice imaged by FMT showed a significant 2-fold decrease in GFR (p < 0.005), and mice treated with Cyclosporine A (80 mg/kg/day) for 14 days showed an expected 40% decrease in GFR (p < 0.05). All imaging results correlated well with ex vivo plasma microplate assays showing increased levels of creatinine and blood urea nitrogen (BUN). In conclusion, FMT imaging of circulating GFR-Vivo 680 in the heart provides a non-invasive fluorescent imaging approach that requires very few mice (3-10 mice per group) to generate consistent GFR measurements and to detect the GFR changes induced by nephrectomy or drug toxicity. As neither blood nor urine sampling is required, and no labor-intensive microplate assays, GFR can be determined quickly after the imaging procedure is completed. These results illustrate the potential of this imaging approach to facilitate the study of kidney disease and the monitoring of drug safety.