Use of a positron myocardial fatty acid metabolism imaging agent and a positron 18F-FDG myocardial glucose imaging agent for PET combined imaging

Abstract

The present application relates to a positron myocardial fatty acid metabolism imaging agent and a positron 18 1. The use of F-FDG myocardial glucose imaging agent for PET combined imaging.

Description

[Technical Field]

[0001] The present application relates to the field of medical reagents, and in particular to positron myocardial fatty acid metabolism imaging agents and positron 18 1. The use of F-FDG myocardial glucose imaging agent for PET combined imaging. [Background technology]

[0002] Assessment of myocardial viability is an essential step before patients with acute myocardial infarction, old myocardial infarction, and total coronary artery occlusion undergo coronary revascularization. Nuclear medicine positron emission tomography (PET) is considered the most effective method for assessing myocardial viability. However, after blood glucose control, 18 Existing myocardial metabolic imaging, which involves injecting F-FDG, takes time (1-4 hours), and is often unable to image patients with insulin resistance. Furthermore, hypoglycemia often occurs during the blood glucose control process, making it clinically impractical. This patent application is based on the existing method involving blood glucose control. 18 Instead of F-FDG myocardial metabolic imaging, subjects were asked to 18 Combined imaging of F-FDG and positron myocardial fatty acid metabolism imaging is performed to assess viable and scarred myocardium. This application proposes a new technical solution for assessing myocardial viability while avoiding various problems associated with blood glucose regulation. Summary of the Invention [Problem to be solved by the invention]

[0003] To the above ends, the present application provides the following:

[0004] 1. Positron myocardial fatty acid metabolism imaging agent and positron to prepare PET combined imaging agent 18 1. Use of an F-FDG myocardial glucose imaging agent, The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: [ka] The positron 18 The chemical formula of the F-FDG myocardial glucose imaging agent used is shown below: [ka] 2. The use according to item 1, wherein the PET combined imaging is used in mammals. 3. The positron myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent was administered to subjects on the same day, Before administering the drug, the subject 18 administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent; 18 Imaging was performed approximately 1 hour after F-FDG injection, and a positron-transmitted myocardial fatty acid metabolism imaging agent was injected immediately after imaging was completed, and imaging was performed immediately. or, First, a positron myocardial fatty acid metabolism imaging agent is administered to a subject and imaging is performed. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent, imaging was performed immediately after injection of positron myocardial fatty acid metabolism imaging agent, and imaging was performed immediately after the end of imaging. 18 F-FDG myocardial glucose imaging agent was injected and imaging was performed approximately 1 hour after injection. The use according to item 2, wherein the subject must fast for at least 4 hours before administering the two imaging agents in sequence. 4. If subjects are administered on the same day, first administer 18 administering and imaging an F-FDG myocardial glucose imaging agent to the subject, and then administering and imaging a positron myocardial fatty acid metabolism imaging agent to the subject; The positron 18Item 4. The use according to Item 3, wherein the ratio of the injection amount (unit: mCi or MBq) of the F-FDG myocardial glucose imaging agent to the positron myocardial fatty acid metabolism imaging agent is 1:x, and x≧1. 5. The use according to item 4, wherein x is 2 to 4. 6. When administered to a subject on the same day, first administer the positron myocardial fatty acid metabolism imaging agent to the subject and perform imaging, and then administer the positron myocardial fatty acid metabolism imaging agent to the subject. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent. the positron myocardial fatty acid metabolism imaging agent and the 18 Item 4. The use according to item 3, wherein the ratio of the injection amount (unit: mCi or MBq) to the F-FDG myocardial glucose imaging agent is 1:x, and x≧1. 7. The use according to item 6, wherein x is 2 to 4. 8. The positron myocardial fatty acid metabolism imaging agent and the positron 18 the F-FDG myocardial glucose imaging agent is administered to the subject on two separate days, On day 1, subjects were given 18 administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent to the subject on the second day; or On the first day, subjects were administered a positron emission tomography (PET) imaging agent and then on the second day, subjects were administered a positron emission tomography (PET) agent and then administered a positron emission tomography (PET) agent. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent. Item 3. The use according to Item 2, wherein the subject is required to fast for at least 4 hours before administration of the imaging agent on each of two days. 9. The use according to item 2, wherein the PET image of the PET combined imaging is used in combination with a myocardial perfusion image to evaluate viable myocardium and scarred myocardium at the site of myocardial infarction, and the myocardial perfusion image is obtained by SPECT or PET myocardial perfusion imaging. 10. Positron Myocardial Fatty Acid Metabolism Imaging Agents and Positrons 18and an F-FDG myocardial glucose imaging agent, The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: [ka] The positron 18 The chemical formula of the F-FDG myocardial glucose imaging agent is shown below. [ka] [Effects of the Invention]

[0005] The beneficial technical effects achieved by the technical solutions of the present application are as follows:

[0006] By adopting the solution of the present application, it is possible to control blood sugar levels. 18 This avoids problems such as low efficiency in F-FDG myocardial metabolic imaging, poor image quality in patients with insulin resistance, and hypoglycemia during blood glucose regulation, improving the clinical practicality of nuclear medicine myocardial metabolic imaging and enabling more patients with myocardial infarction to receive a complete assessment of myocardial viability before undergoing revascularization and determine whether they need to undergo major surgery. [Brief explanation of the drawings]

[0007] [Figure 1a] 1b and 1c are SPECT myocardial blood flow images according to Example 1, and are the results of imaging using 18F-FDG and XTR003 PET in combination. [Figure 2a] 2b and 2c are SPECT myocardial blood flow images according to Example 2, and are the results of imaging using 18F-FDG and XTR003 PET in combination. [Figure 3a-3b] 1 shows the results of imaging using 18F-FDG and XTR003 PET in combination according to Comparative Example 1. [Figure 4a-4b]1 shows the results of imaging using XTR003 and 18F-FDG PET in combination according to Example 3. [Figure 5a-5b] 1 shows the results of imaging using XTR003 and 18F-FDG PET in combination according to Comparative Example 2. [Figure 6a-6b] 1 shows the results of imaging using 18F-FDG and XTR003 PET in combination according to Example 4. [Figure 7a-7b] These are the results of imaging using 18F-FDG and XTR003 PET in combination according to Comparative Example 3. [Figure 8a-8b] 1 shows the results of imaging using 18F-FDG and XTR003 PET in combination according to Comparative Example 4. [Figure 9a-9b] 13 shows the results of imaging using XTR003 and 18F-FDG PET in combination according to Comparative Example 5. DETAILED DESCRIPTION OF THE INVENTION

[0008] Specific embodiments of the present invention will be described in more detail below with reference to the drawings. While specific embodiments of the present invention are illustrated in the drawings, it should be understood that the present application may be embodied in various forms and is not limited to the embodiments set forth herein. Rather, these embodiments are provided to provide a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0009] It should be noted that in this specification and claims, specific terms are used to refer to specific components. Those skilled in the art should understand that engineers may use different nouns to refer to the same component. In this specification and claims, differences in nouns are not used to distinguish between components, but differences in the functions of the components are used as the basis for distinction. As stated throughout this specification and claims, "include" or "comprise" are open terms and should be interpreted as "including but not limited to." The following description is a preferred embodiment for implementing the present invention, but the above description is intended to explain the general principles of this specification and does not limit the scope of the present invention. The protective scope of the present invention is determined by the appended claims.

[0010] As used herein, "substantially free" of a particular component means that the particular component is not intentionally incorporated into the composition and / or is present only as a contaminant or in trace amounts. Thus, the total amount of the particular component resulting from accidental contamination of the composition is less than 0.05%, preferably less than 0.01%. Most preferred are compositions in which the amount of the particular component is undetectable by standard analytical methods.

[0011] As used herein, "a" or "an" may mean one or more. As used in the claims, when used in conjunction with the word "comprises," the words "a" or "an" may mean one or more than one.

[0012] As used herein, the term "or" is used to mean "and / or" unless expressly stated to refer only to alternatives or the alternatives are mutually exclusive, but the content of this application supports a definition that refers only to alternatives and "and / or." As used herein, "another" may mean at least a second or more.

[0013] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for the device, the method used to determine the value, or the variation that exists between study subjects.

[0014] In a first aspect of the present application, a positron myocardial fatty acid metabolism imaging agent and a positron 18 Uses of F-FDG myocardial glucose imaging agents are provided.

[0015] In one specific embodiment, a positron myocardial fatty acid metabolism imaging agent and a positron 18 The use of F-FDG myocardial glucose imaging agent for PET combined imaging is provided.

[0016] The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: [ka]

[0017] In the context of this specification, the compound is codenamed XTR003.

[0018] The positron 18 The chemical formula of the F-FDG myocardial glucose imaging agent is shown below: [ka]

[0019] In the context of this specification, the positron myocardial metabolic imaging method is an effective method for assessing myocardial viability. 18A common method for myocardial metabolic imaging is to inject F-FDG. However, there are some problems with myocardial metabolic imaging, such as the time it takes (1-4 hours), the fact that imaging is often impossible in insulin-resistant patients, and the fact that hypoglycemia often occurs during the blood glucose regulation process, making it of low clinical practicality. This application uniquely involves administering myocardial metabolic imaging to subjects in a fasting state. 18 Combined imaging of myocardial fatty acid metabolism using F-FDG and positron emission tomography (PET) revealed that the metabolic pathways involved in the regulation of blood glucose levels were significantly reduced. 18 It replaces F-FDG myocardial metabolic imaging, where myocardial energy metabolism includes glucose metabolism and fatty acid metabolism. 18 F-FDG myocardial metabolic imaging reflects the energy metabolism of the entire myocardium by converting the fatty acid metabolism portion of the myocardium into a single glucose metabolism portion by adjusting the blood glucose level. 18 Combined imaging of F-FDG and positron myocardial fatty acid metabolism can reflect the overall energy metabolism of the myocardium through both (glucose metabolism + fatty acid metabolism).

[0020] In one specific embodiment, the aforementioned use is provided, wherein said PET combined imaging is used in a mammal.

[0021] In another specific embodiment, The positron myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent was administered to subjects on the same day, Before administering the drug, the subject 18 administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent; 18 The aforementioned use is provided in which imaging is performed approximately one hour after injection of F-FDG, and a positron myocardial fatty acid metabolism imaging agent is injected immediately after completion of imaging, and imaging is performed immediately.

[0022] In yet another specific embodiment, said positron myocardial fatty acid metabolism imaging agent and said positron 18 F-FDG myocardial glucose imaging agent was administered to subjects on the same day, First, a positron myocardial fatty acid metabolism imaging agent is administered to a subject and imaging is performed. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent, imaging was performed immediately after injection of positron myocardial fatty acid metabolism imaging agent, and imaging was performed immediately after the end of imaging. 18 The use is provided, wherein imaging is performed by injecting an F-FDG myocardial glucose imaging agent, and imaging is performed approximately one hour after injection.

[0023] The subject must fast for at least 4 hours before the administration of the two imaging agents in sequence.

[0024] In the context of this specification, the term "administration" refers to various drug intake methods that aim to introduce a drug into the human blood circulation and achieve a sufficient concentration in a specific organ or site to exert an imaging effect before being eliminated by metabolism. The "administration" may be oral or intravenous injection. When administered orally, the imaging agent may be in the form of a tablet, powder, or oral liquid, and when administered intravenously, the imaging agent may be in the form of an injectable liquid.

[0025] In yet another specific embodiment, when administered to a subject on the same day, the subject is first 18 administering and imaging an F-FDG myocardial glucose imaging agent to the subject, and then administering and imaging a positron myocardial fatty acid metabolism imaging agent to the subject; The positron 18The above use is provided, wherein the injection amount (unit: mCi or MBq) ratio of the F-FDG myocardial glucose imaging agent to the positron myocardial fatty acid metabolism imaging agent is 1:x, where x is ≥ 1, preferably 1:2 to 4, and most preferably 1:3. For example, the value of x may be 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, or 4.0.

[0026] In the context of this specification, the value of x can be infinite, but in practice, a value of x between 2 and 4 is most commonly used. This is because this range provides a relatively ideal cost-performance ratio. When x exceeds 4, the imaging effect gradually improves, but the degree of improvement in effect does not linearly correlate with the injection volume.

[0027] In the context of this specification, the value of x must be greater than 1. If it is less than 1, the image noise will be too high and the display will fail.

[0028] In one specific embodiment, when administered to a subject on the same day, the subject is first administered a positron myocardial fatty acid metabolism imaging agent and imaged, and then the subject is administered a positron myocardial fatty acid metabolism imaging agent and imaged. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent. the positron myocardial fatty acid metabolism imaging agent and the 18 The above use is provided, wherein the ratio of injection amount (unit: mCi or MBq) to F-FDG myocardial glucose imaging agent is 1:x, where x is ≥ 1, preferably 1:2 to 4, and most preferably 1:3. For example, the value of x may be 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, or 4.0.

[0029] In the context of this specification, the value of x can be infinite, but in practice, a value of x between 2 and 4 is most commonly used. This is because this range provides relatively ideal cost performance. When x exceeds 4, the imaging effect gradually improves, but the degree of improvement in effect does not linearly correlate with the injection volume.

[0030] In the context of this specification, the value of x must be greater than one. 18 Both F-FDG and XTR003 18 Since it is an F-labeled PET imaging agent, if the value of x is less than 1, the uptake into the myocardium of the earlier injected agent will interfere with the signal of the later injected agent, affecting the accuracy of the latter PET imaging.

[0031] In another specific embodiment, said positron myocardial fatty acid metabolism imaging agent and said positron 18 the F-FDG myocardial glucose imaging agent is administered to the subject on two separate days, On day 1, subjects were given 18 administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent to the subject on the second day; or The above use is provided, wherein the subject is required to fast for at least 4 hours before administration of the imaging agent on each of two days.

[0032] In yet another specific embodiment, said positron myocardial fatty acid metabolism imaging agent and said positron 18 the F-FDG myocardial glucose imaging agent is administered to the subject on two separate days, On the first day, subjects were administered a positron emission tomography (PET) imaging agent and then on the second day, subjects were administered a positron emission tomography (PET) agent and then administered a positron emission tomography (PET) agent. 18 Imaging was performed by administering F-FDG myocardial glucose imaging agent. The above use is provided, wherein the subject is required to fast for at least 4 hours before administration of the imaging agent on each of two days.

[0033] In the context of this specification, the twice-daily and two-day administration methods of the imaging agent are also referred to as the "single-day method" and the "two-day method", respectively. The terms "single-day method" and "two-day method" are general concepts known in the field of imaging agents.

[0034] In yet another specific embodiment, the above-mentioned use is provided, wherein the PET image of the PET combined imaging is used in combination with a myocardial perfusion image to evaluate viable myocardium and scarred myocardium at the site of myocardial infarction, and the myocardial perfusion image is obtained by SPECT or PET myocardial perfusion imaging.

[0035] In the context of this specification, PET is the English abbreviation for "Positron Emission Computed Tomography," which is a relatively advanced clinical imaging technique in the field of nuclear medicine. A common method of PET is to use short-lived radionuclides (e.g., 18 F, 11The aim of this study is to label certain substances, typically those essential for the metabolism of living organisms, such as glucose, proteins, nucleic acids, and fatty acids, with fluorodeoxyglucose (FDG) and inject them into the human body to reflect the metabolic status of the organism through their accumulation in the body, thereby achieving diagnostic purposes. The most commonly used substance in hospitals is fluorodeoxyglucose (FDG). Its mechanism is that the metabolic status of different tissues in the human body varies. Metabolically active malignant tumor tissues have active glucose metabolism and accumulate more glucose. These characteristics are reflected in the images, making it useful for diagnosing and analyzing lesions. In the context of this specification, "myocardial perfusion imaging" refers to a noninvasive test for cardiac disease. Beginning in the 1970s, after nearly 40 years of development, its high diagnostic value has been widely recognized worldwide, and it has now become an important imaging diagnostic method for the diagnosis, efficacy evaluation, and prognosis of coronary artery disease. Myocardial perfusion imaging includes single-photon emitter (SEP) myocardial perfusion imaging and positron emitter (PET) myocardial perfusion imaging. Currently, single-photon emission computed tomography (SPECT) is commonly used in clinical practice. Commonly used myocardial perfusion imaging agents are thallium-201 (TI-201), technetium-99m-sestamibi (Tc-99m-MIBI), and technetium-99m-tetrofosmin.

[0036] In a second aspect of the present application, an imaging agent kit is provided.

[0037] In one specific embodiment, a positron myocardial fatty acid metabolism imaging agent and a positron 18 and an F-FDG myocardial glucose imaging agent, The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: [ka] The positron 18 The chemical formula of the F-FDG myocardial glucose imaging agent is shown below. An imaging agent kit is provided. [ka]

[0038] Based on the above use, the kit provides an amount sufficient for at least one use for a 75 kg human, wherein the positron myocardial fatty acid metabolism imaging agent and the 18 The injection amount (unit: mCi or MBq) ratio of the F-FDG myocardial glucose imaging agent is 1:2 to 5, and the absolute injection amount is, for example, 1 mCi:2 to 5 mCi. Alternatively, 18 The injection amount (unit: mCi or MBq) ratio of the 1 F-FDG myocardial glucose imaging agent to the positron myocardial fatty acid metabolism imaging agent is 1:2-5, and the absolute injection amount is, for example, 1 mCi:2-5 mCi. Example part

[0039] Example 1 Each experiment involved one Bama miniature pig approximately one year old, and the experiment was repeated three times. For example, in the second of the three experiments, a stenosis ring was placed in the left anterior descending coronary artery of a piglet weighing approximately 10 kg, gradually inducing chronic myocardial infarction in the anterior myocardium. Four weeks later, as a comparative experiment, 99mTc-sestamibi SPECT myocardial perfusion imaging was performed in the morning (this imaging is the gold standard for assessing viable and scarred myocardium in the myocardial infarction area, and in this example, it is used to compare the effects of PET imaging). In the afternoon, 18 First, using a 1-day approach of combined F-FDG and XTR003 PET imaging (separated by at least 2 hours from a SPECT performed in the morning, with fasting maintained during the interval). 18 F-FDG PET imaging was performed, followed by XTR003 PET imaging. The injection doses of the two agents were 1 mCi and 2.5 mCi, respectively. 18 XTR003 was injected 1 hour after F-FDG injection, and PET imaging was performed immediately. SPECT myocardial perfusion imaging, 18The results of combined F-FDG and XTR003 PET imaging are shown in Figures 1a-1c. Image interpretation: Figure 1a shows a 99mTc-sestamibi myocardial perfusion image. Myocardial blood flow is reduced in a small area from the apex to the midsegment of the anterior wall, which corresponds to the myocardial infarction area (e.g., the area surrounded by the dotted line). Figure 1b shows the fasting state 18 F-FDG myocardial metabolic image. 18 The level of F-FDG uptake was low, indicating that the myocardial infarction was in a state of low glucose metabolism (e.g., the area enclosed by the dotted line). Figure 1c shows a fasting XTR003 myocardial metabolic image. In the corresponding myocardial infarct area, XTR003 uptake was still moderate, indicating that the myocardial infarct was in a moderate level of fatty acid metabolism (e.g., the area surrounded by the dotted line). Comparing Figures 1a, 1b, and 1c, we found that viable myocardium still existed in the small area of ​​myocardial infarction from the apex to the midsegment of the anterior wall.

[0040] Example 2 Each experiment involved one Bama miniature pig approximately one year old, and the experiment was repeated three times. For example, in the second experiment, a stenosis ring was placed in the left anterior descending coronary artery of a piglet weighing approximately 11 kg, gradually inducing chronic myocardial infarction in the anterior myocardium. Three weeks later, as a comparative experiment, 99mTc-sestamibi SPECT myocardial perfusion imaging was performed in the morning and in the afternoon. 18 First, using a 1-day method of combined F-FDG and XTR003 PET imaging, 18 F-FDG PET imaging was performed, followed by XTR003 PET imaging, with injection doses of 1 mCi and 3.1 mCi, respectively. 18 XTR003 was injected 1 hour after F-FDG injection, and PET imaging was performed immediately. SPECT myocardial perfusion imaging, 18The results of combined F-FDG and XTR003 PET imaging are shown in Figures 2a-2c. Image interpretation: Figure 2a shows a 99mTc-sestamibi myocardial perfusion image. Myocardial perfusion is reduced over a large area from the apex to the base of the heart, which is the myocardial infarction area (e.g., the area enclosed by the box). Figure 2b shows the fasting state 18 F-FDG myocardial metabolic image. 18 F-FDG uptake was absent, indicating that the myocardial infarction was in a state of impaired glucose metabolism (e.g., boxed area). Figure 2c shows a fasting XTR003 myocardial metabolic image. No XTR003 uptake was observed in the corresponding myocardial infarct area, indicating that fatty acid metabolism was absent in the myocardial infarct (e.g., the boxed area). Comparison of Figures 2a, 2b, and 2c revealed the following: Myocardial infarction occurred over a large area from the apex to the base of the anterior wall, and myocardial necrosis and scar myocardium were formed.

[0041] Comparative Example 1: 18 A study of the imaging effect of XTR003 PET imaging after F-FDG PET imaging (injection dose ratio 1:x, where x is less than 1) An animal model of the disease was constructed according to the description in Example 1, and the results were obtained after myocardial perfusion imaging. 18 A one-day imaging method using F-FDGPET and XTR003 PET was performed, where: 18 XTR003 was injected 1 hour after F-FDG injection, and PET imaging was performed immediately. The only difference between this comparative example and Example 1 is that the injection doses of the two agents were 1 mCi and 0.25 mCi, respectively. 18 The results of imaging using F-FDG and XTR003 PET together (the second of three experiments is used as an example) are shown in Figures 3a-3b. Figure 3a shows the fasting state 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal. Figure 3b shows a fasting XTR003 myocardial metabolic image. Compared with Figure 1c, the injection dose of XTR003 was too low, resulting in high image noise and failure of imaging.

[0042] Example 3: First, XTR003 PET imaging was performed, and then 18 A study on F-FDG PET imaging showed that imaging results were equally good. The disease animal model was constructed according to the description in Example 1, and the only difference from Example 1 was the imaging order, specifically, after XTR003 PET imaging, 18 F-FDG PET imaging was performed, and the injection doses of the two drugs were 1 mCi and 3 mCi, respectively. 18 The results of imaging using F-FDG PET are shown in Figures 4a and 4b. Figure 4a is a fasting XTR003 myocardial metabolic image, and compared with Figure 1c, the image quality is normal. Figure 4b shows the fasting state 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal.

[0043] Comparative Example 2: XTR003 After PET imaging, 18 Study of imaging effect when F-FDG PET imaging was performed (injection dose ratio 1:x, x is less than 1) An animal model of the disease was constructed as described in Example 3, and myocardial perfusion imaging was followed by XTR003 PET. 18 A one-day imaging method using F-FDG PET was performed, where 1 hour after XTR003 injection, 18 F-FDG was injected and PET imaging was performed immediately. The only difference between this comparative example and Example 3 is that the injection doses of the two drugs were 1 mCi and 0.25 mCi, respectively. 18 The results of imaging using F-FDG PET are shown in Figures 5a-5b. Figure 5a is a fasting XTR003 myocardial metabolic image, and compared with Figure 4a, the image quality is normal. Figure 5b shows the fasting state 18 F-FDG myocardial metabolic image, and compared with Fig. 4b. 18 The ratio of F-FDG injection dose is too low, resulting in high image noise and imaging failure.

[0044] Example 4: Study of imaging effects using the "2-day method" The disease animal model was constructed according to the description in Example 1. The only difference from Example 1 was that after myocardial perfusion imaging, the "1-day method" was used instead of the "1-day method." 18 The first step was to perform a two-day imaging method using both F-FDG PET and XTR003 PET. 18 The results of combined F-FDG and XTR003 PET imaging are shown in Figures 6a-6b. Figure 6a shows the fasting state 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal. Figure 6b is a fasting XTR003 myocardial metabolic image, and compared with Figure 1c, the image quality is normal.

[0045] Comparative Example 3: Study of the applicability of "no combination use, single imaging agent use" Each experiment involved one Bama miniature pig approximately one year old, and the experiment was repeated three times. For example, in the second experiment, a piglet weighing approximately 10 kg was imaged with two imaging agents separately, rather than with a combination of two. 18 The results of F-FDG and XTR003 PET imaging are shown in Figures 7a and 7b, respectively. Figure 7a shows the fasting state 18 F-FDG myocardial metabolic image, and compared with Fig. 1b, imaging was not possible. Figure 7b shows a fasting XTR003 myocardial metabolic image, which, compared with Figure 1c, shows normal imaging. In normal myocardium, the glucose metabolic rate is low (10%-30%) and the fatty acid metabolic rate is high (60%-90%). 18 Imaging was almost impossible with F-FDG, but imaging was normal with XTR003.

[0046] Comparative Example 4: 18 A study of the imaging effect of XTR003 PET imaging after F-FDG PET imaging (injection dose ratio 1:x, where x is greater than 4) An animal model of the disease was constructed according to the description in Example 1, and after myocardial perfusion imaging, 18 A one-day imaging method using F-FDGPET and XTR003 PET was performed, where: 18 XTR003 was injected 1 hour after F-FDG injection, and PET imaging was performed immediately. The only difference between this comparative example and Example 1 is that the injection doses of the two agents were 1 mCi and 1, 2, 3, 4, and 6 mCi, respectively. 18 The results of imaging using F-FDG and XTR003 PET together (again, the second experiment out of three repeated experiments is shown as an example) are shown in Figures 8a to 9b. Figure 8a shows 18 This shows the change in image quality with changes in the ratio of the two drugs, F-FDG PET and XTR003 PET. Figure 8b shows 18 These are actual images of F-FDG PET and XTR003 PET with varying ratios of the two drugs.

[0047] Comparative Example 5: XTR003 After PET imaging, 18 Study of imaging effect when F-FDG PET imaging was performed (injection volume ratio 1:x, where x is greater than 4) An animal model of the disease was constructed as described in Example 3, and after myocardial perfusion imaging, "XTR003 PET and 18 A one-day imaging method using F-FDG PET was performed, where 1 hour after XTR003 injection, 18F-FDG was injected and PET imaging was performed immediately. The only difference between this comparative example and Example 3 is that the injection doses of the two drugs were 1 mCi and 1, 2, 3, 4, and 6 mCi, respectively. XTR003 PET and 18 The results of imaging using F-FDG are shown in Figures 9a and 9b. Figure 9a shows the XTR003 PET and 18 This is the change in image quality with changing the ratio of the two drugs in F-FDG PET. Figure 9b shows the XTR003 PET and 18 These are actual images of F-FDG PET with varying ratios of the two drugs.

[0048] When imaging using the "one-day method," the more imaging agent used later, the better the imaging effect. However, increasing the injection volume ratio beyond 4 does not further improve image quality. In fact, excessive use significantly increases the cost of using the imaging agent and also increases the radiation risk to the patient. Experiments have shown that imaging results are relatively ideal when the ratio of the imaging agent used first to the imaging agent used later is in the range of 1:2-4.

[0049] Although the present invention has been described above based on the embodiments with reference to the drawings, the present invention is not limited to the above-mentioned specific embodiments and application fields. The above-mentioned specific embodiments are merely examples and are not limiting. A person skilled in the art can create many forms based on the teachings of this specification without departing from the scope of protection of the claims of the present invention, and all of them are within the scope of protection of the present invention.

Claims

1. Positron myocardial fatty acid metabolism imaging agent and positron for preparing a drug for PET combined imaging １８ Use of an F-FDG myocardial glucose imaging agent, The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: 【Chemistry 1】 The positron １８ The chemical formula of the F-FDG myocardial glucose imaging agent is shown below. 【Chemistry 2】

2. The use according to claim 1 , wherein the PET combined imaging is used in a mammal.

3. The positron myocardial fatty acid metabolism imaging agent and the positron １８ F-FDG myocardial glucose imaging agent was administered to the subject on the same day; Before administering the drug, the subject １８ administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent; １８ Imaging was performed approximately one hour after injection of F-FDG, and immediately after the completion of imaging, a positron myocardial fatty acid metabolism imaging agent was injected and imaging was performed immediately. or, First, a positron myocardial fatty acid metabolism imaging agent is administered to a subject and imaging is performed. １８ Imaging was performed by administering the F-FDG myocardial glucose imaging agent, imaging was performed immediately after the injection of the positron myocardial fatty acid metabolism imaging agent, and imaging was performed immediately after the completion of imaging. １８ Imaging is performed by injecting F-FDG myocardial glucose imaging agent, and imaging is performed approximately 1 hour after injection.

3. The use of claim 2, wherein the subject is required to fast for at least four hours before administering the two imaging agents in sequence.

4. If subjects are administered on the same day, first administer １８ administering and imaging an F-FDG myocardial glucose imaging agent to the subject, and then administering and imaging a positron myocardial fatty acid metabolism imaging agent to the subject; The positron １８ 4. The use according to claim 3, wherein the injection ratio of the F-FDG myocardial glucose imaging agent to the positron myocardial fatty acid metabolism imaging agent is 1:x, and x≧1.

5. The use according to claim 4, wherein x is 2 to 4.

6. When administered to a subject on the same day, the subject is first administered a positron myocardial fatty acid metabolism imaging agent and imaged, and then the subject is １８ administering an F-FDG myocardial glucose imaging agent and performing imaging; the positron myocardial fatty acid metabolism imaging agent and the １８ 4. The use according to claim 3, wherein the injection amount ratio with the F-FDG myocardial glucose imaging agent is 1:x, and x≧1.

7. The use according to claim 6, wherein x is 2 to 4.

8. The positron myocardial fatty acid metabolism imaging agent and the positron １８ the F-FDG myocardial glucose imaging agent is administered to the subject on two separate days; On day 1, subjects were administered １８ administering and imaging with an F-FDG myocardial glucose imaging agent, and then administering and imaging with a positron myocardial fatty acid metabolism imaging agent to the subject on the second day; or On the first day, the subject was administered a positron emission tomography (PET) imaging agent and then on the second day, the subject was administered a positron emission tomography (PET) imaging agent. １８ administering an F-FDG myocardial glucose imaging agent and performing imaging; The use according to claim 2, wherein the subject is required to fast for at least 4 hours before administration of the imaging agent on each of two days.

9. The use of claim 2, wherein the PET image of the PET combined imaging is used in combination with a myocardial perfusion image to evaluate viable and scarred myocardium at the site of myocardial infarction, and the myocardial perfusion image is obtained by SPECT or PET myocardial perfusion imaging.

10. Positron Myocardial Fatty Acid Metabolism Imaging Agents and Positrons １８ and an F-FDG myocardial glucose imaging agent, The chemical formula of the positron myocardial fatty acid metabolism imaging agent is shown below: 【Transformation 3】 The positron １８ The chemical formula of the F-FDG myocardial glucose imaging agent is shown below. 【Chemistry 4】

Images