Abstract:This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was conv… Show more
“…FUR not only offers the advantage of expressing organ function in reference to tracer kinetics, but it has also been shown to be independent of patient size, gender, gamma camera, as well as time point and duration of examination [5]. Given the various interindividual differences in mice, this proves to be useful in the murine model as well.…”
Section: Discussionmentioning
confidence: 99%
“…For the calculation of FUR, both kidney and cardiac curves were expressed in units of counts per second. The calculation was based on the equation previously proposed for patient studies [5], namely FUR = P (0) × ( k l + k r )/ID, where k l and k r (per second) are the slopes of the linear uptake [LU] segment of the Patlak-Rutland [PR] plots for the left and right kidneys, respectively. P (0) (counts per second) is the value of the plasma clearance curve P ( t ) at time zero, and it can be obtained by back extrapolation using a mono-exponential fit to P ( t ).…”
Section: Methodsmentioning
confidence: 99%
“…The aim of the present study was to apply 99m Tc-MAG3 imaging for longitudinal follow-up studies of early and, most importantly, long-term kidney function after injury. The fractional uptake rate [FUR] was calculated in analogy to studies in humans [5,6] as a measure of renal clearance using a modified protocol and enabled us to collect valuable information on individual long-term changes. To demonstrate the high accuracy and sensitivity of 99m Tc-MAG3 scintigraphy-based FUR, the study was performed using severe ischemia in a mouse strain with combined immunodeficiency of B cells, T cells, and natural killer cells that is known to confer protection from ischemia-reperfusion injury based on current functional parameters [7].…”
BackgroundExperimental models are essential tools in the development and evaluation of novel treatment options, but the preclinical model of renal ischemia-reperfusion injury is limited to the retrieval of (very) early functional data, leaving the pivotal long-term outcome unknown. The present study applies technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] scintigraphy for the longitudinal follow-up examination of long-term kidney function after renal ischemia-reperfusion injury.MethodsUnilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance.ResultsFUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis.ConclusionsFUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.
“…FUR not only offers the advantage of expressing organ function in reference to tracer kinetics, but it has also been shown to be independent of patient size, gender, gamma camera, as well as time point and duration of examination [5]. Given the various interindividual differences in mice, this proves to be useful in the murine model as well.…”
Section: Discussionmentioning
confidence: 99%
“…For the calculation of FUR, both kidney and cardiac curves were expressed in units of counts per second. The calculation was based on the equation previously proposed for patient studies [5], namely FUR = P (0) × ( k l + k r )/ID, where k l and k r (per second) are the slopes of the linear uptake [LU] segment of the Patlak-Rutland [PR] plots for the left and right kidneys, respectively. P (0) (counts per second) is the value of the plasma clearance curve P ( t ) at time zero, and it can be obtained by back extrapolation using a mono-exponential fit to P ( t ).…”
Section: Methodsmentioning
confidence: 99%
“…The aim of the present study was to apply 99m Tc-MAG3 imaging for longitudinal follow-up studies of early and, most importantly, long-term kidney function after injury. The fractional uptake rate [FUR] was calculated in analogy to studies in humans [5,6] as a measure of renal clearance using a modified protocol and enabled us to collect valuable information on individual long-term changes. To demonstrate the high accuracy and sensitivity of 99m Tc-MAG3 scintigraphy-based FUR, the study was performed using severe ischemia in a mouse strain with combined immunodeficiency of B cells, T cells, and natural killer cells that is known to confer protection from ischemia-reperfusion injury based on current functional parameters [7].…”
BackgroundExperimental models are essential tools in the development and evaluation of novel treatment options, but the preclinical model of renal ischemia-reperfusion injury is limited to the retrieval of (very) early functional data, leaving the pivotal long-term outcome unknown. The present study applies technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] scintigraphy for the longitudinal follow-up examination of long-term kidney function after renal ischemia-reperfusion injury.MethodsUnilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance.ResultsFUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis.ConclusionsFUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.
“…In brief, the FUR is defined as the fractional uptake of a tracer in the blood by an organ as a function of time. FUR is calculated as FUR = P (0)*( k l + k r )/[ID], where P (0) (counts per second) is the magnitude of the plasma clearance curve P ( t ) at time zero, which is obtained by back extrapolation using a mono-exponential fitting of the data to P ( t ), and k l and k r are the slopes of the linear uptake (LU) segment of the Patlak-Rutland (PR) plots for the left and right kidneys [ 32 ]. Fig.…”
BackgroundRadiation-induced nephropathy is still dose limiting in radionuclide therapy of neuroendocrine tumors. We investigated the nephroprotective potential of the angiotensine converting enzyme inhibiting drug enalpril after [177Lu]-DOTATATE therapy in a murine model of radiation-induced nephropathy by renal scintigraphy.At first, the appropriate therapy activity to induce nephropathy was identified. Baseline scintigraphy (n = 12) entailed 12-min dynamic acquisitions after injection of 25 MBq [99mTc]-MAG3, which was followed by radionuclide therapy at four escalating activities of [177Lu]-DOTATATE: group (Gp) 1: 10 MBq; Gp 2: 20 MBq; Gp 3: 40 MBq; Gp 4: 65 MBq. Follow-up [99mTc]-MAG3 scintigraphy was carried out at days 9, 23, 44, and 65. The treatment activity for the intervention arm was selected on the basis of histological examination and declining renal function. In the second part, daily administration by gavage of 10 mg/kg/d enalapril or water (control group) was initiated on the day of radionuclide therapy. Follow-up scintigraphy was carried out at days 9, 23, 44, 65, and 86. We also created a non-therapy control group to detect therapy-independent changes of renal function over time. For all scintigraphies, mean renogram curves were analyzed and the “fractional uptake rate” (FUR; %I.D./min ± SEM) of the tracer by the kidneys was calculated as an index of renal clearance.ResultsAt day 65 of follow-up, no significant change in the FUR relative to baseline (11.0 ± 0.3) was evident in radionuclide therapy groups 1 (11.2 ± 0.5) and 2 (10.1 ± 0.6), but FUR was significantly reduced in groups 3 (8.93 ± 0.6, p < 0.05) and 4 (6.0 ± 0.8, p < 0.01); we chose 40 MBq [177Lu]-DOTATATE (Gp 3) for the intervention study. Here, at the last day of follow-up (day 86), FUR was unaltered in enalapril-treated mice (11.8 ± 0.5) relative to the baseline group (12.4 ± 0.3) and non-therapy group (11.9 ± 0.8), whereas FUR in the control group had undergone a significant decline (9.3 ± 0.5; p < 0.01). Histological examination revealed prevention of kidney damage by enalapril treatment.ConclusionsTreatment with enalapril is effective for nephroprotection during radionuclide therapy with [177Lu]-DOTATATE in mice. Although these results are only limitedly transferable to human studies, enalapril might serve as a promising drug in the mitigation of nephropathy following treatment with [177Lu]-DOTATATE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0219-2) contains supplementary material, which is available to authorized users.
“…Blokhin Cancer Research Center. The level of concentration of both glomerulo- and tubulotropic radiopharmaceuticals in the parenchyma is proved to be a well reproducible measure of the kidney concentration function [ 21 , 24 ]. The statistical analysis of the results was performed using software Statistica 13.0 with the Spearman nonparametric method ( R Sp is a correlation coefficient; the result was considered insignificant at p ≥ 0.05).…”
Study Objective To study the effectiveness of complex monitoring of the kidney function, based on biochemical and radionuclide methods in patients with metastatic renal cell carcinoma (mRCC). Materials and Methods 41 mRCC patients after nephrectomy received nivolumab (n = 23) and interferon-α (n = 18) from 2015 to 2017. At baseline and 2 months after, all patients underwent blood chemistry, urinalysis, Rehberg test, and ELISA to determine serum levels of IL-17A, TGF-β, and erythropoietin. The monitoring of the renal function and urodynamics by complex renal scintigraphy (CRS) was used for all patients using a dual-detector gamma camera and simultaneous data recording in 2 projections. The interpretation of CRS data used the original SENS CRS technology. Study Results Statistically significant correlations were established between IL-17A, TGF-β, and D (excretion rate of 99mTc-technephore from the parenchyma) and Rnfsc (a stable sign of nephrosclerosis), respectively. A significant correlation was established between the parameters of the complex functional monitoring with the prognosis for the risk of renal failure (RF) and efficacy of immunotherapy in mRCC. Conclusions All mRCC patients after nephrectomy were recommended to undergo biochemical monitoring with inclusion of TGF-β and IL-17A, as well as radionuclide monitoring (CRS) to determine the RF risk at an early stage.
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