Methods for assessing mitochondrial function in organs and tissues other than the kidney of a subject

Abstract

The present invention relates to a method for evaluating mitochondrial function in organs and tissues other than the kidneys of a subject, comprising the steps of: calculating the ratio of blood urea nitrogen (BUN) to blood creatinine (CRE) concentration (BUN / CRE) of the subject; and using the calculated ratio (BUN / CRE) to estimate the mitochondrial activity in organs and tissues other than the kidneys of the subject.

Description

Technical Field

[0001] This invention relates to a method for evaluating mitochondrial function in organs and tissues other than the kidneys of a subject. Furthermore, this invention also relates to a data collection method for estimating mitochondrial activity in organs and tissues other than the kidneys of a subject. Background Technology

[0002] Mitochondria are present in almost all cells that make up an organism and are often referred to as the "powerhouses of the cell." Mitochondria play a crucial role in producing adenosine triphosphate (ATP), an essential energy source for cellular activity, from the breakdown of sugars and lipids obtained from ingested food. Therefore, it is easy to imagine that the health of an organism, as a collection of cells, largely depends on the activity of its mitochondria.

[0003] A PET probe is known that uses positron emission tomography (PET) to evaluate mitochondrial function (e.g., non-patent literature 1).

[0004] Existing technical documents

[0005] Non-patent literature

[0006] Non-patent literature 1: J. Nucl. Med., 2020, Vol. 61, pp. 96-103.

[0007] Non-patent literature 2: Life Sciences, 2005, Vol. 76, pp. 1825-1834

[0008] Non-patent literature 3: Clin. Kidney J., 2012, Vol. 5, pp. 187-191

[0009] Non-patent literature 4: Intensive Care Med., 2019, Vol. 45, pp. 1813-1815

[0010] Non-patent literature 5: Nephrology Reviews, 2010, Vol. 2, e11 Summary of the Invention

[0011] [The technical problem that the invention aims to solve]

[0012] The PET probe disclosed in Non-Patent Document 1 (e.g., [ 18The PET probe (F]BCPP-EF) can specifically measure mitochondrial complex I (MC-I). Using this type of PET probe for PET measurements allows for non-invasive measurements, reducing the burden on the subject. However, PET measurements require large-scale equipment and experts in various fields to utilize cyclotrons to manufacture positron-emitting nuclides, label synthetic PET probes, collect image data, and quantitatively interpret the images. Therefore, the method for evaluating mitochondrial function through PET measurements is not a universally applicable method, thus a simpler evaluation method is sought.

[0013] Therefore, the object of the present invention is to provide a method for evaluating mitochondrial function more conveniently.

[0014] [Technical means to solve technical problems]

[0015] The inventors have discovered that the ratio of blood urea nitrogen (BUN) to blood creatinine (CRE), used as an indicator of renal function, unexpectedly shows a strong correlation with mitochondrial activity in organs and tissues other than the kidneys. This invention is based on this novel insight.

[0016] The present invention relates to a method for evaluating mitochondrial function in organs and tissues other than the kidneys of a subject, comprising the steps of: calculating the ratio of blood urea nitrogen (BUN) to blood creatinine (CRE) concentration (BUN / CRE) of the subject; and using the calculated ratio (BUN / CRE) to estimate the mitochondrial activity in organs and tissues other than the kidneys of the subject.

[0017] The proposed BUN / CRE ratio offers a more accurate assessment of renal function compared to existing blood urea nitrogen (BUN) or creatinine (CRE) ratios (e.g., Non-Patent Literature 2-5). However, as described in the following examples, the BUN / CRE ratio lacks universality as an indicator of renal function and exhibits a significant negative correlation with mitochondrial activity in organs and tissues other than the kidneys. The method of this invention, using the BUN / CRE ratio as an indicator, can assess mitochondrial function in organs and tissues other than the kidneys. Furthermore, blood urea nitrogen (BUN) and creatinine (CRE) concentrations can be measured using blood samples collected from the subject, for example, using a general-purpose automated biochemical analyzer, thus allowing for simple implementation.

[0018] Furthermore, the present invention also relates to a data collection method for estimating mitochondrial activity in organs and tissues other than the kidneys of a subject, which includes the step of calculating the ratio (BUN / CRE) of the subject's blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE).

[0019] In the above method, the organs and tissues may be selected from at least one of the brain, brown adipose tissue, heart, pancreas and liver.

[0020] [The effects of the invention]

[0021] According to the present invention, a method for evaluating mitochondrial function can be provided that is more convenient. Attached Figure Description

[0022] Figure 1 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 1 (A): Blood urea nitrogen concentration; Figure 1 (B): Serum creatinine concentration; Figure 1 (C): Creatinine clearance (CCr) and Figure 1 (D): Chart obtained from albumin-creatinine ratio. Each point corresponds to the measured and calculated values ​​of ZDF rats and control rats.

[0023] Figure 2 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 2 (A): Blood urea nitrogen concentration and Figure 2 (B): Chart obtained from serum creatinine concentration. Each point corresponds to the measured and calculated values ​​of 5 / 6Nx rats and control rats.

[0024] Figure 3 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 3 (A): Blood urea nitrogen concentration and Figure 3 (B): Chart obtained from serum creatinine concentration. Each point corresponds to the measured and calculated values ​​for GBM rats and control rats.

[0025] Figure 4 It is plotted based on the values ​​of BUN / CRE. 18 A graph showing the cumulative amount of F]BCPP-BF in the kidneys (SUV). Figure 4 (A) points correspond to the measured and calculated values ​​of ZDF rats and control rats. Figure 4 (B) points correspond to the measured and calculated values ​​of 5 / 6Nx rats and control rats. Figure 4 (C) points correspond to the measured and calculated values ​​of GBM rats and control rats.

[0026] Figure 5 It refers to the values ​​of various biochemical indicators. Figure 5 (A): BUN / CRE; Figure 5 (B): Blood glucose concentration; Figure 5 (C): Total cholesterol concentration in the blood; Figure 5(D): Blood triglyceride concentration and Figure 5 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the brain (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0027] Figure 6 It refers to the values ​​of various biochemical indicators. Figure 6 (A): BUN / CRE; Figure 6 (B): Blood glucose concentration; Figure 6 (C): Total cholesterol concentration in the blood; Figure 6 (D): Blood triglyceride concentration and Figure 6 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in brown adipocytes (tissue) (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0028] Figure 7 It refers to the values ​​of various biochemical indicators. Figure 7 (A): BUN / CRE; Figure 7 (B): Blood glucose concentration; Figure 7 (C): Total cholesterol concentration in the blood; Figure 7 (D): Blood triglyceride concentration and Figure 7 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the heart (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0029] Figure 8 It refers to the values ​​of various biochemical indicators. Figure 8 (A): BUN / CRE; Figure 8 (B): Blood glucose concentration; Figure 8 (C): Total cholesterol concentration in the blood; Figure 8 (D): Blood triglyceride concentration and Figure 8 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the liver (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0030] Figure 9 It refers to the values ​​of various biochemical indicators. Figure 9 (A): BUN / CRE; Figure 9 (B): Blood glucose concentration; Figure 9 (C): Total cholesterol concentration in the blood; Figure 9 (D): Blood triglyceride concentration and Figure 9 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the liver (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0031] Figure 10 It refers to the values ​​of various biochemical indicators. Figure 10 (A): BUN / CRE; Figure 10 (B): Blood glucose concentration; Figure 10 (C): Total cholesterol concentration in the blood; Figure 10 (D): Blood triglyceride concentration and Figure 10 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the kidney (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0032] Figure 11 It is plotted based on the values ​​of BUN / CRE. 18 F]BCPP-BF in various organs ( Figure 11 (A): Heart; Figure 11 (B): Liver and Figure 11 (C): Chart of cumulative amount (SUV) in the kidney. Each point corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats.

[0033] Figure 12 It is plotted based on the values ​​of BUN / CRE. 18 F]BCPP-BF in various organs ( Figure 12 (A): Heart; Figure 12 (B): Liver and Figure 12 (C): Chart of cumulative amount (SUV) in the kidney. Each point corresponds to the measured and calculated values ​​in GBM rats and control rats. Detailed Implementation

[0034] The embodiments of the present invention will now be described in detail. However, the present invention is not limited to the following embodiments.

[0035] [Methods for evaluating mitochondrial function]

[0036] The method for evaluating mitochondrial function in organs and tissues other than the kidneys in this embodiment (hereinafter also referred to as the "evaluation method") includes: a step of calculating the ratio (BUN / CRE) of the blood urea nitrogen concentration (BUN) to the blood creatinine concentration (CRE) of the subject (calculation step); and a step of using the calculated ratio (BUN / CRE) to estimate the mitochondrial activity in organs and tissues other than the kidneys of the subject (estimation step).

[0037] The evaluation method of this embodiment may further include: a step of measuring blood urea nitrogen (BUN) concentration using blood collected from the subject as a sample (BUN measurement step); and / or a step of measuring blood creatinine (CRE) concentration using blood collected from the subject as a sample (CRE measurement step).

[0038] Blood urea nitrogen (BUN) concentration can be measured using conventional methods. Specifically, for example, it can be measured by detecting the nitrogen content in urea using blood collected from the subject, or serum or plasma separated from the blood. The detection of nitrogen in urea can be performed, for example, using commercially available kits. Alternatively, the detection of nitrogen in urea can be performed using automated biochemical analyzers.

[0039] Serum creatinine concentration (CRE) can be measured using conventional methods. Specifically, it can be measured using enzymatic methods (creatine oxidase-sarcosine oxidase-peroxidase), for example, using blood collected from the subject or serum or plasma separated from the blood. Serum creatinine concentration can be measured using commercially available kits, for example. Alternatively, it can be measured using automated biochemical analyzers.

[0040] In the calculation step, the ratio of the subject's blood urea nitrogen concentration (BUN) to blood creatinine concentration (CRE) (BUN / CRE) is calculated. Specifically, for example, the blood urea nitrogen concentration (mg / dL) measured in the BUN measurement step can be divided by the blood creatinine concentration (mg / dL) measured in the CRE measurement step to calculate BUN / CRE.

[0041] In the extrapolation step, the calculated ratio (BUN / CRE) is used to extrapolate mitochondrial activity in organs and tissues other than the kidneys. The BUN / CRE value shows a negative correlation with mitochondrial activity in organs and tissues other than the kidneys; therefore, this correlation can be used in the extrapolation step to extrapolate mitochondrial activity in each organ and tissue (excluding the kidneys) based on the calculated ratio (BUN / CRE).

[0042] Regarding the mitochondrial activity of various organs and tissues (excluding the kidneys) in subjects, for example, the relationship between BUN / CRE values ​​and mitochondrial activity values ​​in various organs and tissues (excluding the kidneys) can be derived based on multiple pre-acquired data sets (BUN / CRE values ​​and mitochondrial activity values ​​in various organs and tissues (excluding the kidneys)). The derived relationship can then be used to estimate the mitochondrial activity of various organs and tissues (excluding the kidneys) in the subjects. More specifically, for example, a correlation can be calculated based on multiple pre-acquired data sets, and the BUN / CRE values ​​obtained from measurements in the subjects can be imported into this correlation to estimate the mitochondrial activity of various organs and tissues (excluding the kidneys) in the subjects. Furthermore, correlations can also be derived using machine learning with large datasets.

[0043] The estimated mitochondrial activity value obtained in the estimation step can also be used to determine whether there is damage or disease in a specific organ or tissue (excluding the kidney) of the subject. In this case, for example, based on one or more data pairs obtained in advance from healthy subjects and one or more data pairs obtained in advance from subjects with damage or disease in a specific organ or tissue (excluding the kidney), the relationship between the BUN / CRE value and the mitochondrial activity value in that organ or tissue is derived. Furthermore, a threshold that can distinguish between healthy subjects and subjects with damage or disease in that organ or tissue is pre-determined. Then, the estimated mitochondrial activity value obtained in the estimation step is compared with this threshold, thereby determining whether there is damage or disease in a specific organ or tissue (excluding the kidney) of the subject. Alternatively, the presence of damage or disease can also be determined based on the results of machine learning from a large dataset.

[0044] Subjects may be, for example, humans, monkeys, mice, and rats, with humans being preferred.

[0045] There are no particular limitations on the organs and tissues that can be evaluated, as long as they are not kidneys. Specific examples include: brain, brown fat cells (brown adipose tissue), heart, pancreas, liver, and muscles. For example, the organs and tissues that can be evaluated may be selected from at least one of the following: brain, brown fat cells (brown adipose tissue), heart, pancreas, and liver.

[0046] [Data Collection Methods]

[0047] The data collection method of this embodiment is a method for collecting data to estimate mitochondrial activity in organs and tissues other than the kidneys of a subject, and includes at least the step of calculating the ratio of the subject's blood urea nitrogen (BUN) to blood creatinine (CRE) (BUN / CRE). As described above, the BUN / CRE value obtained by the data collection method of this embodiment can be used to estimate mitochondrial activity in organs and tissues other than the kidneys of a subject.

[0048] The data collection method of this embodiment may further include: a step of measuring blood urea nitrogen (BUN) concentration using blood collected from the subject as a sample (BUN measurement step); and / or a step of measuring blood creatinine (CRE) concentration using blood collected from the subject as a sample (CRE measurement step).

[0049] Example

[0050] The present invention will now be described in more detail with reference to embodiments. However, the present invention is not limited thereto.

[0051] [Experimental Example 1: Evaluation of the activity of mitochondrial complex I]

[0052] (Synthesis of PET probes)

[0053] According to the method described in non-patent literature (J. Labelled Comp. Radiopharm., 2013, Vol. 56, No. 11, pp. 553-561), the following formula is synthesized: 18 The final product obtained had a radiochemical purity of 99.0% and a specific activity of 73.4 GBq / μmol.

[0054]

[0055] Known [ 18 F]BCPP-BF can be used to detect mitochondrial complex I (MC-I). 18 F]BCPP-BF specifically accumulates in MC-I, becoming an accumulation level directly proportional to the MC-I activity of the target organ or tissue. Therefore, [ 18 The cumulative amount of F]BCPP-BF is used as an indicator to evaluate the MC-I activity of the target organs and tissues.

[0056] To pinpoint the location of the pancreas, a probe (D-[ ]) was prepared to identify the highly expressed amino acid transporter (LAT-1) in the pancreas of small animals. 11 C]MT). D-[ 11 C]MT was synthesized using the method described in Example 1 of International Publication No. 2005 / 115971. The resulting final product had a radiochemical purity of 100.0% and a specific activity of 56.4 GBq / μmol.

[0057] (ZDF rat)

[0058] Male Zucker Lepr, exhibiting symptoms similar to adult-onset type 2 diabetes, was purchased from Charles River Laboratories Japan Co., Ltd. fa / Lepr fa Rats (hereinafter also referred to as "ZDF rats") underwent PET measurements at 5, 8, 16, and 26 weeks of age. Male Zucker Lepr rats were purchased from Charles River Laboratories Japan Co., Ltd. fa / + rats (hereinafter also referred to as "control rats") were used as controls.

[0059] (5 / 6Nx rats)

[0060] As a model of chronic kidney disease, 5 / 6 nephrectomy rats (removed at 7 weeks of age, hereinafter referred to as "5 / 6 Nx rats") were purchased from Japan SLC Co., Ltd., and PET measurements were performed at 2 weeks and 14 weeks after removal. As a control, sham-operated rats without nephrectomy were used.

[0061] (GBM rat)

[0062] As an acute kidney disease model, nephritis rats (treated at 7 weeks of age; hereinafter referred to as "GBM rats") administered with anti-glomerular basement membrane antibody (anti-GBM antibody) were purchased from Japan SLC Co., Ltd., and PET measurements were performed at 2 weeks and 6 weeks after treatment. As a control, sham-operated rats without anti-GBM antibody were used.

[0063] (PET Measurement)

[0064] Rats were anesthetized with isoflurane and fixed in the support of an animal PET camera (SHR-38000, manufactured by Hamamatsu Photonics Co., Ltd.). After 15 minutes of transmittance measurement for absorption correction, approximately 20 MBq / 0.5 mL of D-[[] was administered via the rat's tail vein. 11 C]MT, and emission measurements were performed for 60 minutes. Subsequently, approximately 20 MBq / 0.5 mL of [ ] was administered via the tail vein of the rat. 18 F]BCPP-BF, conduct 60 minutes of launch measurements.

[0065] After the PET measurement is completed, in the D-[ 11 C]MT identifies the designated target region in the pancreas using cumulative PET images 40–60 minutes after administration, and calculates […]. 18 The cumulative amount of BCPP-BF in the target region. Then, the calculated cumulative amount was normalized to the individual's body weight and the administered radiation energy, as [F]. 18 [F] The cumulative amount of BCPP-BF in the pancreas (cumulative radioactive energy (SUV)). Regarding organs and tissues other than the pancreas and brain, respectively, through […18 Target regions were identified in various organs and tissues using PET cumulative images of F]BCPP-BF, and the cumulative radiation energy (SUV) was calculated using the same method as for the pancreas. For the brain, the SUV was calculated immediately after PET measurement by removing the brain from the rat.

[0066] [Experimental Example 2: Determination of Biochemical Indicators]

[0067] Blood was collected from rats immediately after PET scans, and the concentrations of blood urea nitrogen, creatinine, glucose, total cholesterol, triglycerides, and insulin were measured using an automated biochemical analyzer (Hitachi High-Tech Corporation 7180). The BUN / CRE ratio was calculated using the following formula.

[0068] BUN / CRE = Blood urea nitrogen concentration (mg / dL) / Blood creatinine concentration (mg / dL)

[0069] Urine from rats immediately after PET measurements was collected, and the concentrations of albumin and creatinine in the urine were measured using an automated biochemical analyzer (Hitachi High-Tech Corporation 7180). Creatinine clearance (CCr) and albumin-to-creatinine ratio (ACR) were calculated using the following formulas.

[0070] CCr = (urinary creatinine concentration (mg / dL) × urine volume at each time (dL)) / serum creatinine concentration (mg / dL)

[0071] ACR = Urinary albumin concentration (mg / dL) / Urinary creatinine concentration (mg / dL)

[0072] [Experimental Example 3: Correlation Analysis of MC-I Activity and Biochemical Indicators]

[0073] The correlation between the cumulative radiation energy (SUV) data obtained in Experiment 1 and the biochemical index data obtained in Experiment 2 was analyzed.

[0074] Figure 1 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 1 (A): Blood urea nitrogen concentration; Figure 1 (B): Serum creatinine concentration; Figure 1 (C): Creatinine clearance (CCr) and Figure 1 (D): Chart obtained from albumin-creatinine ratio. Each point corresponds to the measured and calculated values ​​of ZDF rats and control rats.

[0075] Figure 2 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 2 (A): Blood urea nitrogen concentration and Figure 2 (B): Chart obtained from serum creatinine concentration. Each point corresponds to the measured and calculated values ​​of 5 / 6Nx rats and control rats.

[0076] Figure 3 It plots the values ​​of various biochemical indicators based on the BUN / CRE values. Figure 3 (A): Blood urea nitrogen concentration and Figure 3 (B): Chart obtained from serum creatinine concentration. Each point corresponds to the measured and calculated values ​​for GBM rats and control rats.

[0077] In ZDF rats, serum urea nitrogen and serum creatinine concentrations showed significant positive and negative correlations with BUN / CRE levels, respectively. Figure 1 (A) and (B)), but no correlation was found with the values ​​of creatinine clearance and albumin-creatinine ratio, which directly reflect renal function. Figure 1 (C) and (D)). In 5 / 6Nx rats, serum urea nitrogen and serum creatinine concentrations showed no correlation with BUN / CRE values. Figure 2 (A) and (B)). Similarly, in GBM rats, serum urea nitrogen and serum creatinine concentrations did not show a correlation with BUN / CRE values. Figure 3 (A) and (B)). Based on these results, it is concluded that the BUN / CRE value is not a universal indicator of renal function.

[0078] Figure 4 It is plotted based on the values ​​of BUN / CRE. 18 A graph showing the cumulative amount of F]BCPP-BF in the kidneys (SUV). Figure 4 (A) points correspond to the measured and calculated values ​​of ZDF rats and control rats. Figure 4 (B) points correspond to the measured and calculated values ​​of 5 / 6Nx rats and control rats. Figure 4 (C) points correspond to the measured and calculated values ​​of GBM rats and control rats.

[0079] Regarding [ 18 The accumulation of BCPP-BF (SUV) in the kidney, as evaluated by MC-I activity, showed a significant negative correlation with the BUN / CRE value in ZDF rats. Figure 4 (A)), but no correlation was observed in 5 / 6Nx rats and GBM rats. Figure 4 (B) and (C)). Based on these results, it is concluded that the BUN / CRE value still does not have universality as an indicator of renal function.

[0080] Figure 5 It refers to the values ​​of various biochemical indicators. Figure 5(A): BUN / CRE; Figure 5 (B): Blood glucose concentration; Figure 5 (C): Total cholesterol concentration in the blood; Figure 5 (D): Blood triglyceride concentration and Figure 5 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the brain (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0081] pass[ 18 The accumulation of BCPP-BF (SUV) in the brains of ZDF rats was evaluated based solely on the BUN / CRE ratio. Figure 5 (A) and the value of blood triglyceride concentration ( Figure 5 (D) shows a significant negative correlation.

[0082] Figure 6 It refers to the values ​​of various biochemical indicators. Figure 6 (A): BUN / CRE; Figure 6 (B): Blood glucose concentration; Figure 6 (C): Total cholesterol concentration in the blood; Figure 6 (D): Blood triglyceride concentration and Figure 6 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in brown adipocytes (tissue) (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0083] pass[ 18 The accumulation of BCPP-BF (SUV) in brown adipocytes (tissue) of ZDF rats was evaluated based solely on the BUN / CRE value. Figure 6 (A)), the value of blood triglyceride concentration ( Figure 6 (D) and the value of blood insulin concentration ( Figure 6 (E) shows a significant negative correlation.

[0084] Figure 7 It refers to the values ​​of various biochemical indicators. Figure 7 (A): BUN / CRE; Figure 7 (B): Blood glucose concentration; Figure 7 (C): Total cholesterol concentration in the blood; Figure 7 (D): Blood triglyceride concentration and Figure 7 (E): Blood insulin concentration) plotted [ 18A graph showing the cumulative amount of BCPP-BF in the heart (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0085] pass[ 18 The accumulation of BCPP-BF (SUV) in the heart of ZDF rats was evaluated based solely on the BUN / CRE value. Figure 7 (A) shows a significant negative correlation.

[0086] Figure 8 It refers to the values ​​of various biochemical indicators. Figure 8 (A): BUN / CRE; Figure 8 (B): Blood glucose concentration; Figure 8 (C): Total cholesterol concentration in the blood; Figure 8 (D): Blood triglyceride concentration and Figure 8 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the liver (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0087] pass[ 18 The accumulation of BCPP-BF (SUV) in the liver of ZDF rats was evaluated based solely on the BUN / CRE ratio. Figure 8 (A) shows a significant negative correlation.

[0088] Figure 9 It refers to the values ​​of various biochemical indicators. Figure 9 (A): BUN / CRE; Figure 9 (B): Blood glucose concentration; Figure 9 (C): Total cholesterol concentration in the blood; Figure 9 (D): Blood triglyceride concentration and Figure 9 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the liver (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0089] pass[ 18 The accumulation of BCPP-BF (SUV) in the liver of ZDF rats was evaluated based solely on the BUN / CRE ratio. Figure 9 (A) and the value of blood triglyceride concentration ( Figure 9 (D) shows a significant negative correlation.

[0090] Figure 10 It refers to the values ​​of various biochemical indicators. Figure 10 (A): BUN / CRE; Figure 10 (B): Blood glucose concentration; Figure 10 (C): Total cholesterol concentration in the blood; Figure 10 (D): Blood triglyceride concentration and Figure 10 (E): Blood insulin concentration) plotted [ 18 A graph showing the cumulative amount of BCPP-BF in the kidney (SUV). Each point corresponds to the measured and calculated values ​​in ZDF rats and control rats.

[0091] pass[ 18 The accumulation of BCPP-BF (SUV) in the kidneys of ZDF rats was evaluated based solely on the BUN / CRE ratio. Figure 10 (A) shows a significant negative correlation.

[0092] Figure 11 It is plotted based on the values ​​of BUN / CRE. 18 F]BCPP-BF in various organs ( Figure 11 (A): Heart; Figure 11 (B): Liver and Figure 11 (C): Chart of cumulative amount (SUV) in the kidney. Each point corresponds to the measured and calculated values ​​in 5 / 6Nx rats and control rats.

[0093] Although the value of BUN / CRE is related to […] 18 The accumulation of BCPP-BF (SUV) in 5 / 6Nx rats showed a significant negative correlation with MC-I activity in the heart and liver. Figure 11 (A) and (B)), but no significant correlation was found with renal MC-I activity. Figure 11 (C)).

[0094] Figure 12 It is plotted based on the values ​​of BUN / CRE. 18 F]BCPP-BF in various organs ( Figure 12 (A): Heart; Figure 12 (B): Liver and Figure 12 (C): Chart of cumulative amount (SUV) in the kidney. Each point corresponds to the measured and calculated values ​​in GBM rats and control rats.

[0095] Although the value of BUN / CRE is related to […] 18 The accumulation of BCPP-BF (SUV) in GBM rats showed a significant negative correlation with MC-I activity in the heart and liver. Figure 12 (A) and (B)), but no significant correlation was found with renal MC-I activity. Figure 12 (C)).

[0096] (Summarize)

[0097] As shown in the above experimental examples, the BUN / CRE value did not demonstrate universality as an indicator of renal function. On the other hand, it can be seen that the BUN / CRE value is related to […]. 18 The accumulation of F]BCPP-BF (SUV) showed a significant negative correlation with MC-I activity in organs and tissues other than the kidneys, and can be used as an evaluation index of mitochondrial function in various organs (organs and tissues other than the kidneys).

Claims

1. A data collection method for estimating mitochondrial activity in the heart and / or liver of a subject, wherein, This includes steps to calculate the ratio of blood urea nitrogen (BUN) to blood creatinine (CRE) concentration (BUN / CRE) in the subject.

Images