Methods for assessing mitochondrial function in non-renal organs and tissues of a subject

Abstract

To provide a method for making it possible to evaluate mitochondrial function in a more convenient manner.SOLUTION: The method for assessing a mitochondrial function of an organ and tissue other than a kidney of a subject includes the steps of calculating a ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in the subject and using the calculated ratio (BUN / CRE) to estimate mitochondrial activity in the organ and tissue other than the subject's kidney.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for assessing mitochondrial function in non-renal organs and tissues of a subject.The present invention also relates to a method for collecting data to estimate mitochondrial activity in non-renal organs and tissues of a subject. [Background technology]

[0002] Mitochondria are present in almost all cells that make up living organisms, and are sometimes called the "powerhouses of cells." Mitochondria play an important role in producing adenosine triphosphate (ATP), an essential energy source for cellular activity, from sugars and lipids that are broken down from ingested food. For this reason, it is not difficult to imagine that the health of a living organism, which is a collection of cells, depends heavily on the activity of mitochondria.

[0003] Positron emission tomography (PET) probes for evaluating mitochondrial function using PET are known (eg, Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J. Nucl. Med., 2020, vol. 61, pp. 96-103. [Non-Patent Document 2] Life Sciences, 2005, Vol. 76, pp. 1825-1834 [Non-Patent Document 3] Clin.Kidney J.,2012,5,pp.187-191 [Non-Patent Document 4] Intensive Care Med., 2019, Vol. 45, pp. 1813-1815 [Non-Patent Document 5] Nephrology Reviews, 2010, Vol. 2, e11 Summary of the Invention [Problem to be solved by the invention]

[0005] The PET probe disclosed in Non-Patent Document 1 (e.g., 18 [F]BCPP-EF) can specifically measure mitochondrial complex-I (MC-I). By using such a PET probe to perform PET measurements, non-invasive measurements are possible, reducing the burden on subjects. On the other hand, PET measurements require large-scale facilities and experts in various fields for the production of positron-emitting nuclides using a cyclotron, labeling and synthesis of PET probes, collection of image data, and quantitative analysis of images. For this reason, the method of evaluating mitochondrial function using PET measurements is by no means a highly versatile method, and an evaluation method that can be performed more easily is required.

[0006] Therefore, an object of the present invention is to provide a method for evaluating mitochondrial function more simply and easily. [Means for solving the problem]

[0007] The present inventors have unexpectedly found that the ratio of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE), which is used as an index for evaluating renal function, (BUN / CRE) shows a good correlation with mitochondrial activity in organs and tissues other than the kidney. The present invention is based on this novel finding.

[0008] The present invention relates to a method for assessing mitochondrial function in organs and tissues other than the kidney of a subject, comprising the steps of calculating a ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in a subject, and estimating mitochondrial activity in the organs and tissues other than the kidney of the subject using the calculated ratio (BUN / CRE).

[0009] It has been proposed that the BUN / CRE value may be able to evaluate renal function more accurately than the conventionally used blood urea nitrogen concentration (BUN) or blood creatinine concentration (CRE) values ​​(e.g., Non-Patent Documents 2-5). However, as described in the Examples below, the BUN / CRE value is not universal as an evaluation index of renal function, and on the other hand, it shows a significant negative correlation with mitochondrial activity of organs and tissues other than the kidney. The method according to the present invention uses the BUN / CRE value as an index, and therefore can evaluate the mitochondrial function of organs and tissues other than the kidney. In addition, the blood urea nitrogen concentration (BUN) and blood creatinine concentration (CRE) can be measured using, for example, a commonly used biochemical automatic analyzer using blood collected from a subject as a sample, and therefore can be easily performed.

[0010] The present invention also relates to a data collection method for estimating mitochondrial activity in organs and tissues other than the kidney of a subject, comprising the step of calculating the ratio of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) (BUN / CRE) in the subject.

[0011] In the above-mentioned method, the organ and tissue may be at least one selected from the group consisting of the brain, brown adipose tissue, heart, pancreas, and liver. Effect of the Invention

[0012] According to the present invention, a method for evaluating mitochondrial function more simply and easily can be provided. [Brief description of the drawings]

[0013] [Figure 1] The graphs show plots of the values ​​of each biochemical index (Figure 1(A): blood urea nitrogen concentration, Figure 1(B): blood creatinine concentration, Figure 1(C): creatinine clearance rate (CCr), and Figure 1(D): albumin creatinine ratio) against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Diagram 2] The graphs show the values ​​of each biochemical index (FIG. 2(A): blood urea nitrogen concentration and FIG. 2(B): blood creatinine concentration) plotted against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats. [Diagram 3] The graphs show the values ​​of each biochemical index (FIG. 3(A): blood urea nitrogen concentration and FIG. 3(B): blood creatinine concentration) plotted against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in GBM rats and control rats. [Figure 4] 4 is a graph showing the accumulation (SUV) of [18F]BCPP-BF in the kidney plotted against the BUN / CRE value. Each plot in FIG. 4(A) corresponds to the measured and calculated values ​​in ZDF rats and control rats. Each plot in FIG. 4(B) corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats. Each plot in FIG. 4(C) corresponds to the measured and calculated values ​​in GBM rats and control rats. [Diagram 5] These are graphs plotting the accumulation (SUV) of [18F]BCPP-BF in the brain against the values ​​of each biochemical index (Fig. 5(A): BUN / CRE, Fig. 5(B): blood glucose concentration, Fig. 5(C): blood total cholesterol concentration, Fig. 5(D): blood triglyceride concentration, and Fig. 5(E): blood insulin concentration). Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 6] The graphs show the accumulation (SUV) of [18F]BCPP-BF in brown adipocytes (tissues) plotted against the values ​​of each biochemical index (Fig. 6(A): BUN / CRE, Fig. 6(B): blood glucose concentration, Fig. 6(C): blood total cholesterol concentration, Fig. 6(D): blood triglyceride concentration, and Fig. 6(E): blood insulin concentration). Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 7]7(A): BUN / CRE, FIG. 7(B): blood glucose concentration, FIG. 7(C): ​​blood total cholesterol concentration, FIG. 7(D): blood triglyceride concentration, and FIG. 7(E): blood insulin concentration. Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 8] 8(A): BUN / CRE, FIG. 8(B): blood glucose concentration, FIG. 8(C): blood total cholesterol concentration, FIG. 8(D): blood triglyceride concentration, and FIG. 8(E): blood insulin concentration. Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 9] 9(A): BUN / CRE, FIG. 9(B): blood glucose concentration, FIG. 9(C): blood total cholesterol concentration, FIG. 9(D): blood triglyceride concentration, and FIG. 9(E): blood insulin concentration. Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 10] The graphs show the accumulation (SUV) of [18F]BCPP-BF in the kidney plotted against the values ​​of each biochemical index (Figure 10(A): BUN / CRE, Figure 10(B): blood glucose concentration, Figure 10(C): blood total cholesterol concentration, Figure 10(D): blood triglyceride concentration, and Figure 10(E): blood insulin concentration). Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats. [Figure 11] 11 shows graphs plotting the accumulation (SUV) of [18F]BCPP-BF in each organ (FIG. 11(A): heart, FIG. 11(B): liver, and FIG. 11(C): kidney) against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats. [Figure 12]12(A) shows the accumulation (SUV) of [18F]BCPP-BF in each organ (FIG. 12(A): heart, FIG. 12(B): liver, and FIG. 12(C): kidney) plotted against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in GBM rats and control rats. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiment.

[0015] [Method for evaluating mitochondrial function] The method for evaluating mitochondrial function in organs and tissues other than the kidney of a subject according to this embodiment (hereinafter also simply referred to as the "evaluation method") includes a step of calculating the ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in the subject (calculation step), and a step of estimating mitochondrial activity in the organs and tissues other than the kidney of the subject using the calculated ratio (BUN / CRE) (estimation step).

[0016] The evaluation method according to this embodiment may further include a step of measuring a blood urea nitrogen concentration (BUN) using blood collected from a subject as a sample (BUN measurement step), and / or a step of measuring a blood creatinine concentration (CRE) using blood collected from a subject as a sample (CRE measurement step).

[0017] The blood urea nitrogen concentration (BUN) can be measured according to a conventional method. Specifically, for example, the blood collected from the subject, or the serum or plasma separated from the blood, can be used to detect the nitrogen contained in the urea. The detection of the nitrogen contained in the urea can be carried out, for example, by using a commercially available kit. The detection of the nitrogen contained in the urea may also be carried out using an automatic biochemical analyzer or the like.

[0018] The blood creatinine concentration (CRE) can be measured according to a conventional method. Specifically, for example, the blood collected from the subject, or the serum or plasma separated from the blood, can be measured by an enzyme method (creatinase-sarcosine oxidase-peroxidase method). The blood creatinine concentration can be measured, for example, by using a commercially available kit. The blood creatinine concentration may also be measured using an automatic biochemical analyzer or the like.

[0019] In the calculation step, the ratio (BUN / CRE) of the blood urea nitrogen concentration (BUN) to the blood creatinine concentration (CRE) in the subject is calculated. Specifically, for example, the BUN / CRE can be calculated by dividing the blood urea nitrogen concentration (mg / dL) measured in the BUN measurement step by the blood creatinine concentration (mg / dL) measured in the CRE measurement step.

[0020] In the estimation step, the calculated ratio (BUN / CRE) is used to estimate mitochondrial activity in the subject's organs and tissues other than the kidney. Since the value of BUN / CRE shows a negative correlation with mitochondrial activity in the organs and tissues other than the kidney, in the estimation step, the mitochondrial activity in each organ and tissue (excluding the kidney) of the subject can be estimated from the calculated ratio (BUN / CRE) by utilizing this correlation.

[0021] The mitochondrial activity in each organ and tissue (excluding the kidney) of the subject can be estimated, for example, by deriving a relationship between the BUN / CRE value and the mitochondrial activity value in each organ and tissue (excluding the kidney) from a plurality of data pairs (BUN / CRE value and mitochondrial activity value in each organ and tissue (excluding the kidney)) acquired in advance, and then deriving the relationship and the BUN / CRE value measured in the subject. More specifically, for example, a correlation equation is calculated from a plurality of data pairs acquired in advance, and the mitochondrial activity in each organ and tissue (excluding the kidney) of the subject can be estimated by introducing the BUN / CRE value measured in the subject into the correlation equation. In addition, the correlation may be derived by machine learning using a huge amount of data.

[0022] The estimated value of mitochondrial activity obtained in the estimation step can also be used to determine whether or not the subject has a disorder or disease in a specific organ and tissue (excluding the kidney). In this case, for example, from one or more data pairs previously obtained from a healthy subject and one or more data pairs previously obtained from a subject having a disorder or disease in a specific organ and tissue (excluding the kidney), the relationship between the BUN / CRE value and the mitochondrial activity value in the organ and tissue is derived, and a threshold value capable of distinguishing between a healthy subject and a subject having a disorder or disease in the organ and tissue is determined in advance. Then, by comparing the estimated value of mitochondrial activity obtained in the estimation step with the threshold value, it is possible to determine whether or not the subject has a disorder or disease in a specific organ and tissue (excluding the kidney). In addition, it is also possible to determine whether or not the subject has a disorder or disease based on the results of machine learning from a huge amount of data.

[0023] The subject may be, for example, a human, monkey, mouse, or rat, but is preferably a human.

[0024] The organs and tissues to be evaluated are not particularly limited as long as they are organs and tissues other than the kidney, and specific examples include the brain, brown fat cells (brown fat tissue), heart, pancreas, liver, and muscle. The organs and tissues to be evaluated may be at least one selected from the group consisting of the brain, brown fat cells (brown fat tissue), heart, pancreas, and liver.

[0025] [Data collection method] The data collection method according to the present embodiment is a method for collecting data for estimating mitochondrial activity of organs and tissues other than the kidney of a subject, and includes at least a step of calculating the ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in the subject. As described above, the value of BUN / CRE obtained by the data collection method according to the present embodiment can be used to estimate mitochondrial activity of organs and tissues other than the kidney of a subject.

[0026] The data collection method according to this embodiment may further include a step of measuring a blood urea nitrogen concentration (BUN) using blood collected from a subject as a sample (BUN measurement step), and / or a step of measuring a blood creatinine concentration (CRE) using blood collected from a subject as a sample (CRE measurement step). EXAMPLES

[0027] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these.

[0028] [Test Example 1: Evaluation of mitochondrial complex-I activity] (PET probe synthesis) According to the method described in the non-patent literature (J. Labeled Comp. Radiopharm., 2013, Vol. 56, No. 11, pp. 553-561), 18 The radiochemical purity of the final product was 99.0% and the specific activity was 73.4 GBq / μmol. [ka]

[0029] [ 18 It is known that [F]BCPP-BF can be used to detect mitochondrial complex-I (MC-I). 18 F]BCPP-BF specifically accumulates in MC-I, and the amount of accumulation is proportional to the MC-I activity in the target organ or tissue. 18 The amount of [F]BCPP-BF accumulated can be used as an indicator to evaluate MC-I activity in target organs and tissues.

[0030] To identify the location of the pancreas, a probe (D-[ 11 C]MT) was prepared. D-[ 11 C]MT was synthesized by the method described in Example 1 of WO 2005 / 115971. The radiochemical purity of the final product obtained was 100.0%, and the specific activity was 56.4 GBq / μmol.

[0031] (ZDF rat) Male Zucker Leprosy Develops a Pathology Similar to Type II Diabetes in Adult Humans fa / Lepr fa Rats (hereinafter referred to as "ZDF rats") were purchased from Charles River Japan, Inc. and subjected to PET measurements at the ages of 5, 8, 16 and 26 weeks. fa / + rats (hereinafter also referred to as "control rats") were purchased from Charles River Japan, Inc. and used.

[0032] (5 / 6NxRat) As a chronic kidney disease model, rats with 5 / 6 of the kidney removed (removal procedure at 7 weeks of age, hereafter referred to as "5 / 6Nx rats") were purchased from Japan SLC Co., Ltd. and used for PET measurement 2 and 14 weeks after removal. Sham-operated rats without kidney removal were used as controls.

[0033] (GBM rats) As an acute kidney disease model, nephritic rats administered with anti-GBM antibody (anti-GBM antibody) (treated at 7 weeks of age; hereafter also referred to as "GBM rats") were purchased from Japan SLC Co., Ltd. and subjected to PET measurements at 2 and 6 weeks after administration. Sham-operated rats not administered anti-GBM antibody were used as controls.

[0034] (PET measurement) The rats were anesthetized with isoflurane and fixed in the gantry of an animal PET camera (SHR-38000, Hamamatsu Photonics Co., Ltd.). After 15 minutes of transmission measurement for absorption correction, approximately 20 MBq / 0.5 mL of D-[ 11 After administration of [C]MT, emission measurements were performed for 60 minutes. 18 F]BCPP-BF was administered and emissions were measured for 60 min.

[0035] After PET measurement, D-[ 11 A region of interest was set in the pancreas identified from the PET accumulation image 40-60 minutes after administration of [C]MT, and the [ 18 The amount of F]BCPP-BF accumulated was then calculated. The calculated amount of accumulation was then normalized by the body weight and the amount of radioactivity administered for each individual, and the amount of [F]BCPP-BF accumulated in the pancreas was calculated. 18 The accumulation of F]BCPP-BF was defined as the standardized average radiation exposure (SUV). 18Regions of interest were set in each organ and tissue identified in the PET images of [F]BCPP-BF, and the SUV was calculated in the same manner as for the pancreas. The SUV in the brain was calculated by extracting the brain from the rats immediately after PET measurement.

[0036] [Test Example 2: Measurement of biochemical indicators] Immediately after PET measurement, blood was collected from the rats, and the blood urea nitrogen concentration, blood creatinine concentration, blood glucose concentration, blood total cholesterol concentration, blood triglyceride concentration, and blood insulin concentration were measured using an automatic biochemical analyzer (Hitachi High-Tech 7180). The BUN / CRE value was calculated using the following formula. BUN / CRE = Blood urea nitrogen concentration (mg / dL) / Blood creatinine concentration (mg / dL)

[0037] Immediately after PET measurement, urine samples were collected from the rats, and the urinary albumin and creatinine concentrations were measured using an automatic biochemical analyzer (Hitachi High-Tech 7180). Creatinine clearance rate (CCr) and albumin creatinine ratio (ACR) were calculated using the following formulas. CCr = (urine creatinine concentration (mg / dL) × urine volume per hour (dL)) / blood creatinine concentration (mg / dL) ACR = urinary albumin concentration (mg / dL) / urinary creatinine concentration (mg / dL)

[0038] [Test Example 3: Correlation analysis between MC-I activity and biochemical indicators] The correlation between the data on radioactivity uptake (SUV) obtained in Test Example 1 and the data on biochemical indices obtained in Test Example 2 was analyzed.

[0039] Figure 1 is a graph plotting the values ​​of each biochemical index (Figure 1(A): blood urea nitrogen concentration, Figure 1(B): blood creatinine concentration, Figure 1(C): creatinine clearance rate (CCr), and Figure 1(D): albumin creatinine ratio) against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0040] Figure 2 is a graph plotting the values ​​of each biochemical index (Figure 2(A): blood urea nitrogen concentration and Figure 2(B): blood creatinine concentration) against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats.

[0041] Figure 3 is a graph plotting the values ​​of each biochemical index (Figure 3(A): blood urea nitrogen concentration and Figure 3(B): blood creatinine concentration) against the BUN / CRE value. Each plot corresponds to the measured and calculated values ​​in GBM rats and control rats.

[0042] In ZDF rats, the blood urea nitrogen concentration and blood creatinine concentration showed significant positive and negative correlations with the BUN / CRE ratio (Fig. 1(A) and (B)), but did not show correlations with the creatinine clearance rate and albumin creatinine ratio, which directly reflect renal function (Fig. 1(C) and (D)). In 5 / 6Nx rats, the blood urea nitrogen concentration and blood creatinine concentration did not show correlations with the BUN / CRE ratio (Fig. 2(A) and (B)). Similarly, in GBM rats, the blood urea nitrogen concentration and blood creatinine concentration did not show correlations with the BUN / CRE ratio (Fig. 3(A) and (B)). These results suggest that the BUN / CRE ratio is not a universal indicator of renal function.

[0043] Figure 4 shows the relationship between BUN / CRE and kidney function. 18 4 is a graph plotting the accumulation (SUV) of [F]BCPP-BF. Each plot in FIG. 4(A) corresponds to the measured and calculated values ​​in ZDF rats and control rats. Each plot in FIG. 4(B) corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats. Each plot in FIG. 4(C) corresponds to the measured and calculated values ​​in GBM rats and control rats.

[0044] [ 18Renal MC-I activity evaluated by [F]BCPP-BF uptake (SUV) showed a significant negative correlation with the BUN / CRE value in ZDF rats (Figure 4(A)), but not in 5 / 6Nx rats or GBM rats (Figures 4(B) and (C)). These results suggest that the BUN / CRE value is not universally applicable as an index of renal function.

[0045] Figure 5 shows the relationship between the value of each biochemical index (Figure 5(A): BUN / CRE, Figure 5(B): blood glucose concentration, Figure 5(C): blood total cholesterol concentration, Figure 5(D): blood triglyceride concentration, and Figure 5(E): blood insulin concentration) and the [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0046] [ 18 Brain MC-I activity in ZDF rats, assessed by [F]BCPP-BF accumulation (SUV), showed a significant negative correlation only with the BUN / CRE value (Figure 5(A)) and blood triglyceride concentration value (Figure 5(D)).

[0047] Figure 6 shows the relationship between the amount of BUN / CRE in brown fat cells and the amount of insulin in brown fat tissue. 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0048] [ 18 MC-I activity in brown adipocytes (tissues) of ZDF rats, assessed by [F]BCPP-BF accumulation (SUV), showed a significant negative correlation only with the BUN / CRE values ​​(Figure 6(A)), blood triglyceride concentrations (Figure 6(D)), and blood insulin concentrations (Figure 6(E)).

[0049] FIG. 7 shows the relationship between the value of each biochemical index (FIG. 7(A): BUN / CRE, FIG. 7(B): blood glucose concentration, FIG. 7(C): ​​blood total cholesterol concentration, FIG. 7(D): blood triglyceride concentration, and FIG. 7(E): blood insulin concentration) and the effect of [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0050] [ 18 Cardiac MC-I activity in ZDF rats evaluated by [F]BCPP-BF accumulation (SUV) showed a significant negative correlation only with the BUN / CRE value (Figure 7(A)).

[0051] FIG. 8 shows the relationship between the values ​​of each biochemical index (FIG. 8(A): BUN / CRE, FIG. 8(B): blood glucose concentration, FIG. 8(C): blood total cholesterol concentration, FIG. 8(D): blood triglyceride concentration, and FIG. 8(E): blood insulin concentration). pancreas To 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0052] [ 18 F]BCPP-BF accumulation (SUV) in ZDF rats pancreas The MC-I activity in the rats showed a significant negative correlation only with the BUN / CRE value (FIG. 8(A)).

[0053] FIG. 9 shows the relationship between the value of each biochemical index (FIG. 9(A): BUN / CRE, FIG. 9(B): blood glucose concentration, FIG. 9(C): blood total cholesterol concentration, FIG. 9(D): blood triglyceride concentration, and FIG. 9(E): blood insulin concentration) and the effect of [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0054] [ 18MC-I activity in the liver of ZDF rats, assessed by [F]BCPP-BF accumulation (SUV), showed a significant negative correlation only with the BUN / CRE value (Figure 9(A)) and the blood triglyceride concentration value (Figure 9(D)).

[0055] FIG. 10 shows the relationship between the value of each biochemical index (FIG. 10(A): BUN / CRE, FIG. 10(B): blood glucose concentration, FIG. 10(C): blood total cholesterol concentration, FIG. 10(D): blood triglyceride concentration, and FIG. 10(E): blood insulin concentration) and the effect of [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, where each plot corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0056] [ 18 Renal MC-I activity in ZDF rats evaluated by F]BCPP-BF accumulation (SUV) showed a significant negative correlation only with the BUN / CRE value (Figure 10(A)).

[0057] FIG. 11 shows the relationship between the BUN / CRE value and the amount of [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF. Each plot corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats.

[0058] The BUN / CRE value is 18 F]BCPP-BF accumulation (SUV) showed a significant negative correlation with MC-I activity in the heart and liver of 5 / 6Nx rats (Figures 11(A) and (B)), but did not show a significant correlation with MC-I activity in the kidney (Figure 11(C)).

[0059] FIG. 12 shows the relationship between the BUN / CRE value and the amount of [ 18 1 is a graph plotting the accumulation (SUV) of [F]BCPP-BF, with each plot corresponding to the measured and calculated values ​​in GBM rats and control rats.

[0060] The BUN / CRE value is 18 F]BCPP-BF accumulation (SUV) showed a significant negative correlation with MC-I activity in the heart and liver of GBM rats (Figures 12(A) and (B)), but did not show a significant correlation with MC-I activity in the kidney (Figure 12(C)).

[0061] (summary) As shown in the above test example, the BUN / CRE value was not found to be universal as an evaluation index of renal function. 18 It was found that the accumulation (SUV) of [F]BCPP-BF showed a significant negative correlation with MC-I activity in organs and tissues other than the kidney, indicating that it can be used as an evaluation index for mitochondrial function in each organ (organs and tissues other than the kidney).

Claims

1. A method for determining a ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in a subject, and estimating mitochondrial activity in organs and tissues other than the kidney of the subject using the calculated ratio (BUN / CRE), A method for evaluating mitochondrial function in organs and tissues other than the kidney of a subject, wherein the organs and tissues are at least one selected from the group consisting of the brain, brown adipose tissue, heart, pancreas and liver.

2. A data collection method for estimating mitochondrial activity in organs and tissues other than the kidney of a subject, comprising the step of calculating a ratio (BUN / CRE) of blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) in the subject, The method as described above, wherein the organ and tissue is at least one selected from the group consisting of the brain, brown adipose tissue, heart, pancreas, and liver.

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