Positron emission tomography (PET) myocardial fatty acid metabolism imaging agents and positron emission tomography (PET) 18 Applications of F-FDG myocardial glucose imaging agent in combined PET imaging

Abstract

The present application relates to positron myocardial fatty acid metabolism imaging agents and positron 18 Use of F-FDG myocardial glucose imaging agents for PET co-imaging.

Description

[0001] This case involves an application filed on March 16, 2023, entitled "Positron Emission Imaging Agent for Myocardial Fatty Acid Metabolism and Positron Emission Imaging Agent". 18 This is a divisional application of the case with application number CN202310255399.7 concerning the use of F-FDG myocardial glucose imaging agent in combined PET imaging. Technical Field

[0002] This application relates to the field of medical reagents, and in particular to positron emission tomography (PET) myocardial fatty acid metabolism imaging agents and positron emission tomography (PET) imaging agents. 18 The use of F-FDG myocardial glucose imaging agent for combined PET imaging. Background Technology

[0003] Assessing viable myocardium is a necessary step for patients with acute myocardial infarction, old myocardial infarction, and total coronary artery occlusion before coronary revascularization. Nuclear medicine positron emission tomography (PET) myocardial metabolic imaging is considered one of the most effective methods for assessing viable myocardium, but current methods involve injecting the drug after blood glucose regulation. 18 The time required for F-FDG myocardial metabolic imaging is too long (1-4 hours), and it is often impossible to perform imaging on patients with insulin resistance. Furthermore, hypoglycemia frequently occurs during the blood glucose regulation process, resulting in limited clinical applicability. This patent application addresses this by having subjects undergo imaging under fasting conditions. 18 Combined F-FDG and positron emission tomography myocardial fatty acid metabolism imaging to replace existing blood glucose regulation methods. 18 F-FDG myocardial metabolic imaging is used to assess viable myocardium and scarred myocardium. This application aims to propose a new technical solution that can eliminate the various problems caused by blood glucose regulation, while providing an assessment of viable myocardium. Summary of the Invention

[0004] For the purposes stated above, this application provides: 1. Positron emission tomography (PET) myocardial fatty acid metabolism imaging agents and positron emission tomography (PET) 18 The use of F-FDG myocardial glucose imaging agent in the preparation of pharmaceutical agents for combined PET imaging, among which, The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: ; The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: .

[0005] 2. The use as described in item 1, wherein the PET combined imaging is applied to mammals.

[0006] 3. The use as described in item 2, wherein, The positron emission tomography myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent was administered to the subjects on the same day. First administer to the subject. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. 18 Imaging was performed approximately one hour after F-FDG injection. Immediately after imaging, a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent was injected, followed by immediate imaging. or Imaging was performed on the subject first using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, followed by administration of... 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed immediately by positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, and then immediately after imaging was completed. 18 F-FDG myocardial glucose imaging agent was used, and imaging was performed approximately one hour after injection. The subjects were required to fast for at least 4 hours before the two imaging agents were administered sequentially.

[0007] 4. The use as described in item 3, wherein when administered to a subject on the same day, the subject is first administered... 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. The positron 18 The ratio of the injection dose (in mCi or MBq) of the F-FDG myocardial glucose imaging agent to that of the positron emission tomography myocardial fatty acid metabolism imaging agent is 1:x, and x ≥ 1.

[0008] 5. The use as described in item 4, where x is 2 to 4.

[0009] 6. The use as described in item 3, wherein, when administered to a subject on the same day, the subject is first subjected to imaging with a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, and then the subject is administered... 18 Imaging was performed using F-FDG myocardial glucose imaging agent. The positron emission tomography myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injection dose (unit: mCi or MBq) of F-FDG myocardial glucose imaging agent is 1:x, and x≥1.

[0010] 7. The use as described in item 6, where x is 2 to 4.

[0011] 8. The use as described in item 2, wherein the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and the positron emission tomography (PET) 18The F-FDG myocardial glucose imaging agent was administered to the subjects on two separate days. Administered to the subject on the first day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging with a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent on the second day, or... On the first day of administration, the subject was given a positron emission tomography (PET) imaging agent for myocardial fatty acid metabolism, followed by administration on the second day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent; The subjects were required to fast for at least 4 hours on two separate days before receiving the imaging agent.

[0012] 9. The use as described in item 2, wherein the PET images from the combined PET imaging and the myocardial perfusion images are used in combination to assess the condition of viable myocardium and scarred myocardium at the site of myocardial infarction, wherein the myocardial perfusion images are obtained from SPECT or PET myocardial perfusion imaging.

[0013] 10. An imaging reagent kit comprising a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and a positron emission tomography (PET) sensor. 18 F-FDG myocardial glucose imaging agent; The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: ; The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: .

[0014] The beneficial technical effects achieved by the technical solution of this application Using the solution proposed in this application, blood sugar regulation can be eliminated. 18 The problems of low efficiency, poor image quality in patients with insulin resistance, and hypoglycemic events during blood glucose regulation caused by F-FDG myocardial metabolic imaging should be addressed. This will improve the clinical applicability of nuclear medicine myocardial metabolic imaging, allowing more myocardial infarction patients to obtain a complete assessment of viable myocardium before undergoing revascularization, and then determine the necessity of major surgery. Attached Figure Description

[0015] Figure 1a For SPECT myocardial perfusion images based on Example 1, and Figure 1b-1c for 18 Results of combined F-FDG and XTR003 PET imaging.

[0016] Figure 2a For SPECT myocardial perfusion images based on Example 2, and Figures 2b-2c for 18Results of combined F-FDG and XTR003 PET imaging.

[0017] Figures 3a-3b According to Comparative Example 1 18 Results of combined F-FDG and XTR003 PET imaging.

[0018] Figures 4a-4b According to Example 3, XTR003 and 18 F-FDG PET combined imaging results.

[0019] Figures 5a-5b Based on Comparative Example 2, XTR003 and 18 F-FDG PET combined imaging results.

[0020] Figures 6a-6b According to Example 4 18 Results of combined F-FDG and XTR003 PET imaging.

[0021] Figure 7a and 7b According to Comparative Example 3 18 Imaging results of F-FDG and XTR003 PET. Detailed Implementation

[0022] Specific embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While specific embodiments of the invention are shown in the drawings, it should be understood that the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the invention and to fully convey the scope of the invention to those skilled in the art.

[0023] It should be noted that certain terms are used in the specification and claims to refer to specific components. Those skilled in the art will understand that different terms may be used to refer to the same component. This specification and claims do not distinguish components based on differences in terminology, but rather on differences in function. The terms "comprising" or "including" used throughout the specification and claims are open-ended and should be interpreted as "comprising but not limited to." The following descriptions are preferred embodiments for carrying out the invention; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of the invention. The scope of protection of this invention is determined by the appended claims.

[0024] As used herein, "substantially free of" with respect to a particular component is used to indicate that the particular component was not intentionally formulated into the composition and / or is present only as a contaminant or in trace amounts. Therefore, the total amount of the particular component resulting from any accidental contamination of the composition is less than 0.05%, preferably less than 0.01%. Most preferably, the composition is in which the amount of the particular component is undetectable by standard analytical methods.

[0025] As used in this specification, "a" or "an" may mean one or more. As used in the claims, when used with the word "comprising," the word "a" or "an" may mean one or more.

[0026] The term “or” is used in the claims to mean “and / or” unless it is explicitly stated that it refers only to an alternative or that the alternatives are mutually exclusive, although the content of this application supports the definition of referring only to an alternative and “and / or”. As used herein, “another” can mean at least a second or more.

[0027] Throughout this application, the term “about” is used to indicate a value that includes the inherent variation of the error of the apparatus, the method used to determine that value, or the variation that exists between subjects under study.

[0028] This application provides, in its first aspect, a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and a positron emission tomography (PET) imaging agent. 18 The use of F-FDG myocardial glucose imaging agent in the preparation of pharmaceutical agents for combined PET imaging.

[0029] In one specific embodiment, a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and a positron emission tomography (PET) imager are provided. 18 The use of F-FDG myocardial glucose imaging agent in combined PET imaging, among which, The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: In the context of this specification, the compound is referred to as XTR003.

[0030] The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: .

[0031] In the context of this specification, the positron emission tomography (PET) method for myocardial metabolic imaging is an effective method for assessing viable myocardium, and is commonly used after blood glucose regulation via injection. 18F-FDG is used for myocardial metabolic imaging. Problems include the excessively long imaging time (1-4 hours), frequent inability to perform imaging on insulin-resistant patients, and frequent hypoglycemic events during blood glucose regulation, resulting in limited clinical applicability. This application creatively proposes a method to perform imaging on subjects in a fasting state. 18 Combined F-FDG and positron emission tomography myocardial fatty acid metabolism imaging to replace existing blood glucose regulation methods. 18 F-FDG myocardial metabolic imaging. Here, myocardial energy metabolism includes glucose metabolism and fatty acid metabolism, regulating blood glucose... 18 F-FDG myocardial metabolic imaging modulates blood glucose levels to convert the fatty acid metabolism of the myocardium into glucose metabolism, thus representing the overall energy metabolism of the myocardium. 18 F-FDG and positron emission tomography combined imaging of myocardial fatty acid metabolism can simultaneously display the total energy metabolism of the myocardium through (glucose metabolism + fatty acid metabolism).

[0032] In one specific embodiment, the foregoing use is provided, wherein the combined PET imaging is applied to mammals.

[0033] In yet another specific embodiment, the aforementioned uses are provided, wherein, The positron emission tomography myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent was administered to the subjects on the same day. First administer to the subject. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. 18 Imaging was performed approximately one hour after F-FDG injection. Imaging was performed immediately after the injection of a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent.

[0034] In another specific embodiment, the aforementioned use is provided, wherein the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and positron emission tomography (PET) 18 F-FDG myocardial glucose imaging agent was administered to the subjects on the same day. Imaging was performed on the subject first using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, followed by administration of... 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed immediately by positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, and then immediately after imaging was completed. 18 F-FDG myocardial glucose imaging agent was used, and imaging was performed approximately one hour after injection.

[0035] The subjects were required to fast for at least 4 hours before the two imaging agents were administered sequentially.

[0036] In the context of this specification, "administration" can refer to various means of drug intake aimed at enabling the drug to enter the bloodstream and reach a sufficient concentration in a specific organ or site to exert its imaging effect before being metabolized and eliminated. "Administration" can be oral or intravenous. When administered orally, the imaging agent may be in the form of tablets, powders, or oral liquids; when administered intravenously, the imaging agent may be in the form of an injection.

[0037] In another specific embodiment, the above-described use is provided, wherein when administered to a subject on the same day, the subject is first administered... 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. The positron 18 The ratio of the injection dose (in mCi or MBq) of the F-FDG myocardial glucose imaging agent to the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is 1:x, where x ≥ 1; preferably 1:2 to 4, and most preferably 1:3. As an example, the value of x can be 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, or 4.0.

[0038] In the context of this specification, the value of x can be infinite, but in actual use, the value of x = 2 to 4 is most frequently used. This is because a relatively ideal performance-cost ratio is achieved within this range. When x is greater than 4, although the imaging effect gradually improves, the degree of improvement is not linearly related to the injection dose.

[0039] In the context of this specification, the value of x must be greater than 1; a value less than 1 will result in excessive image noise and display failure.

[0040] In one specific embodiment, the above-described use is provided, wherein, when administered to a subject on the same day, the subject is first given a positron emission tomography (PET) cardiomyocyte fatty acid metabolism imaging agent for imaging, and then the subject is given... 18 Imaging was performed using F-FDG myocardial glucose imaging agent. The positron emission tomography myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injection dose (unit: mCi or MBq) of the F-FDG myocardial glucose imaging agent is 1:x, x≥1; preferably 1:2~4; most preferably 1:3. As an example, the value of x can be 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, 4.0.

[0041] In the context of this specification, the value of x can be infinite, but in actual use, the value of x = 2 to 4 is most frequently used. This is because a relatively ideal performance-cost ratio is achieved within this range. When x is greater than 4, although the imaging effect gradually improves, the degree of improvement is not linearly related to the injection dose.

[0042] In the context of this specification, the value of x must be greater than 1. Because 18 F-FDG and XTR003 are both 18 When the x value of an F-labeled PET imaging agent is less than 1, the uptake in the myocardium of the first recipient will interfere with the signal of the second recipient, affecting the accuracy of the latter's PET imaging.

[0043] In yet another specific embodiment, the above-described use is provided, wherein the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and the positron emission tomography (PET) are used together. 18 The F-FDG myocardial glucose imaging agent was administered to the subjects on two separate days. Administered to the subject on the first day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging with a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent on the second day. The subjects were required to fast for at least 4 hours on two separate days before receiving the imaging agent.

[0044] In another specific embodiment, the above-described use is provided, wherein the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and the positron emission tomography (PET) are used together. 18 The F-FDG myocardial glucose imaging agent was administered to the subjects on two separate days. On the first day of administration, the subject was given a positron emission tomography (PET) imaging agent for myocardial fatty acid metabolism, followed by administration on the second day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent; The subjects were required to fast for at least 4 hours on two separate days before receiving the imaging agent.

[0045] In the context of this specification, the administration methods of the imaging agent, namely, administering the agent twice a day and administering it on two separate days, are also referred to as the "one-day method" and the "two-day method," respectively. The terms "one-day method" and "two-day method" are generally known concepts in the field of imaging agents.

[0046] In another specific embodiment, the above-mentioned use is provided, wherein the PET images from the combined PET imaging and the myocardial perfusion images are used in combination to assess the condition of viable myocardium and scarred myocardium at the site of myocardial infarction, wherein the myocardial perfusion images are obtained from SPECT or PET myocardial perfusion imaging.

[0047] In the context of this specification, PET is an abbreviation for "Positron Emission Computed Tomography"; this is a relatively advanced clinical imaging technique in the field of nuclear medicine. The general method of PET involves labeling a substance, typically essential for biological metabolism such as glucose, proteins, nucleic acids, and fatty acids, with a short-lived radioactive isotope (e.g., positron emission tomography). 18 F, 11 (C, etc.) After being injected into the human body, the accumulation of this substance during metabolism reflects the state of life's metabolic activities, thereby achieving the purpose of diagnosis. The substance mainly used by hospitals is fluorodeoxyglucose, abbreviated as FDG. Its mechanism is that the metabolic state of different tissues in the human body is different. In malignant tumor tissues with high metabolism, glucose metabolism is vigorous and more accumulates. These characteristics can be reflected in images, thereby enabling the diagnosis and analysis of lesions. In the context of this instruction manual, "myocardial perfusion imaging" is a non-invasive examination for heart disease. It originated in the 1970s. After nearly 40 years of development, its enormous diagnostic value has been widely accepted worldwide, becoming an important imaging method for the diagnosis, efficacy evaluation, and prognosis of coronary heart disease. Myocardial perfusion imaging includes single-photon emission and positron emission tomography (PET) myocardial perfusion imaging. Currently, single-photon emission computed tomography (SPECT) is the most commonly used in clinical practice. Commonly used myocardial perfusion imaging agents are thallium-201 (TI-201), technetium-99m-methoxyisocyanate (Tc-99m-MIBI), and technetium-99m-tetraphosphine.

[0048] In a second aspect, this application provides an imaging agent kit.

[0049] In one embodiment, an imaging agent kit is provided, comprising a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and a positron emission tomography (PET) sensor. 18 F-FDG myocardial glucose imaging agent; The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: .

[0050] Based on the above-described uses, the kit provides a quantity sufficient for at least a single use in a human body weighing 75 kg, wherein the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is present in conjunction with the... 18The ratio of the injection dose (in mCi or MBq) of the F-FDG myocardial glucose imaging agent is 1:2-5, with the absolute injection dose being, for example, 1 mCi: 2-5 mCi; or the positron emission tomography (PET) assay... 18 The ratio of the injection dose (in mCi or MBq) of the F-FDG myocardial glucose imaging agent to the positron emission tomography myocardial fatty acid metabolism imaging agent is 1:2-5; the absolute injection dose is, for example, 1 mCi:2-5 mCi.

[0051] Example Section Example 1 Each experiment used one approximately one-year-old Bama miniature pig, and the experiment was repeated three times. Taking the second experiment as an example: the piglet weighed about 10 kg and underwent a constriction ring placement surgery in the left anterior descending coronary artery, gradually inducing chronic myocardial infarction in the anterior wall myocardium. Four weeks later, as a control experiment, 99mTc-Sestamibi SPECT myocardial perfusion imaging was performed in the morning (this imaging is the gold standard for evaluating viable myocardium and scarred myocardium at the site of myocardial infarction, and in this example, it was used for comparison of PET imaging effects); in the afternoon, a one-day method was used. 18 Combined F-FDG and XTR003 PET imaging (at least 2 hours after the SPECT performed in the morning, with fasting maintained during the interval), first 18 Following F-FDG PET imaging, XTR003 PET imaging was performed. The injection doses of the two agents were 1 mCi and 2.5 mCi, respectively. 18 F-FDG involves injecting XTR003 one hour after the initial injection, followed immediately by PET imaging.

[0052] SPECT myocardial perfusion images 18 The combined imaging results of F-FDG and XTR003 PET are as follows: Figures 1a-1c As shown. Image interpretation: Figure 1a .99mTc-Sestamibi myocardial perfusion image: A small area of ​​decreased myocardial perfusion from the apex to the mid-segment of the anterior wall, which is the area of ​​myocardial infarction (as shown by the dashed box); Figure 1b .fasting 18 F-FDG myocardial metabolic image: corresponding to the myocardial infarction area 18 Low F-FDG uptake indicates that myocardial infarction is in a low-level glucose metabolism state (as shown in the dashed box area); Figure 1c Fasting XTR003 myocardial metabolism image: Moderate XTR003 uptake is still present in the corresponding myocardial infarction area, indicating that the myocardial infarction is in a moderate fatty acid metabolism state (as shown in the dashed box area); through Figure 1a , Figure 1b and Figure 1c The comparison showed that there was still viable myocardium in the small area of ​​myocardial infarction from the apex to the middle of the anterior wall.

[0053] Example 2 Each experiment used one approximately one-year-old Bama miniature pig, and the experiment was repeated three times. Taking the second experiment as an example: the pig weighed about 11 kg and underwent a constriction ring placement surgery in the left anterior descending coronary artery, gradually inducing chronic myocardial infarction in the anterior wall myocardium. Three weeks later, as a control experiment, 99mTc-Sestamibi SPECT myocardial perfusion imaging was performed in the morning; in the afternoon, a one-day method was used. 18 Combined imaging with F-FDG and XTR003 PET, first 18 Following F-FDG PET imaging, XTR003 PET imaging was performed. The injection doses of the two agents were 1 mCi and 3.1 mCi, respectively; among them, in 18 F-FDG involves injecting XTR003 one hour after the initial injection, followed immediately by PET imaging.

[0054] SPECT myocardial perfusion images 18 The combined imaging results of F-FDG and XTR003 PET are as follows: Figures 2a-2c As shown. Image interpretation: Figure 2a .99mTc-Sestamibi myocardial perfusion image: A large area of ​​decreased myocardial perfusion from the apex to the basal segment, indicating the myocardial infarction area (as shown in the box). Figure 2b .fasting 18 F-FDG myocardial metabolic image: No corresponding myocardial infarction area 18 F-FDG uptake indicates that myocardial infarction is in a state of glucose metabolism absence (as shown in the boxed area); Figure 2c Fasting XTR003 myocardial metabolism image: No XTR003 uptake is observed in the corresponding myocardial infarction area, indicating that the myocardial infarction is in a state of no fatty acid metabolism (as shown in the selected area); pass Figure 2a , Figure 2b and Figure 2c The comparison showed that the large area of ​​myocardial infarction from the apex to the basal segment of the anterior wall was myocardial necrosis and had formed scarred myocardium.

[0055] Comparative Example 1 Study: First 18 Imaging effect of F-FDG PET imaging followed by XTR003 PET imaging (injection ratio 1:x, where x is less than 1). A disease animal model was constructed according to the description in Example 1, and a "one-day method" was implemented after myocardial perfusion imaging.18 "Combined imaging of F-FDG PET and XTR003 PET", in which 18 F-FDG involves injecting XTR003 1 hour after injection, followed immediately by PET imaging; the only difference between this comparative example and Example 1 is that the injection doses of the two agents are 1 mCi and 0.25 mCi, respectively. 18 The combined imaging results of F-FDG and XTR003 PET (using the second experiment out of three as an example) are as follows: Figures 3a-3b As shown in the figure: Figure 3a .fasting 18 F-FDG myocardial metabolic images, and Figure 1b In comparison, the image quality is normal.

[0056] Figure 3b Fasting XTR003 myocardial metabolic images, and Figure 1c In contrast, the low injection dose of XTR003 resulted in excessive image noise and imaging failure.

[0057] Example 3 Study: XTR003 PET imaging followed by 18 F-FDG PET imaging also provides excellent imaging results.

[0058] The disease animal model was constructed according to the description in Example 1, with the only difference being the imaging order; specifically, XTR003 PET imaging was performed first, followed by... 18 F-FDG PET imaging, the injection doses of the two agents mentioned above were 1 mCi and 3 mCi, respectively; XTR003 and 18 The combined PET imaging results of F-FDG are as follows: Figures 4a-4b As shown in the figure: Figure 4a Fasting XTR003 myocardial metabolic images, and Figure 1c In comparison, the image quality is normal; Figure 4b .fasting 18 F-FDG myocardial metabolic images, and Figure 1b In comparison, the image quality is normal.

[0059] Comparative Example 2 Study: XTR003 PET Imaging Followed by 18 Imaging effect of F-FDG PET imaging (injection ratio 1:x, where x is less than 1) A disease animal model was constructed according to the description in Example 3, and a "one-day XTR003 PET and" method was performed after the myocardial perfusion phenomenon. 18 "F-FDG PET combined imaging", where XTR003 was injected 1 hour after injection. 18F-FDG, followed immediately by PET imaging; the only difference between this comparative example and Example 3 is that the injection doses of the two agents are 1 mCi and 0.25 mCi, respectively; 18 The combined imaging results of F-FDG and XTR003 PET are as follows: Figures 5a-5b As shown in the figure: Figure 5a Fasting XTR003 myocardial metabolic images, and Figure 4a In comparison, the image quality is normal.

[0060] Figure 5b .fasting 18 F-FDG myocardial metabolic images, and Figure 4b In comparison, because 18 The F-FDG injection dose ratio was too low, resulting in excessive image noise and imaging failure.

[0061] Example 4 Study: Imaging effect of the "two-day method" The disease animal model was constructed according to the description in Example 1, the only difference being that the "two-day method" was implemented after the myocardial perfusion phenomenon. 18 "Combined imaging of F-FDG PET and XTR003 PET", rather than "one-day method". 18 The combined imaging results of F-FDG and XTR003 PET are as follows: Figures 6a-6b As shown in the figure: Figure 6a .fasting 18 F-FDG myocardial metabolic images, and Figure 1b In comparison, the image quality is normal.

[0062] Figure 6b Fasting XTR003 myocardial metabolic images, and Figure 1c In comparison, the image quality is normal.

[0063] Comparative Example 3 investigates the applicability of "not using in combination, using a single imaging agent". Each experiment used a Bama miniature pig that was about 1 year old, and the experiment was repeated three times. Taking the second experiment in the three experiments as an example: the pig weighed about 10 kilograms, and the two injections were used for imaging separately, rather than combined imaging. 18 The imaging results of F-FDG and XTR003 PET are as follows: Figure 7a and Figure 7b As shown in the figure: Figure 7a .fasting 18 F-FDG myocardial metabolic images, and Figure 1b In comparison, it does not show up.

[0064] Figure 7bFasting XTR003 myocardial metabolic images, and Figure 1c In comparison, the imaging is normal.

[0065] Because normal myocardium has a low glucose metabolism rate (10%-30%) and a high fatty acid metabolism rate (60%-90%), 18F-FDG is almost undetectable, while XTR003 can be detected normally.

[0066] It should be noted that when using the "one-day method" for imaging, the more developer used later, the better the imaging effect; however, excessive use will significantly increase the cost of developer. Experiments have shown that a developer ratio of 1:2 to 4 used later is ideal.

[0067] Although embodiments of the present invention have been described above in conjunction with the accompanying drawings, the present invention is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the guidance of this specification and without departing from the scope of protection of the claims of the present invention, and all of these are within the scope of protection of the present invention.

Claims

1. Positron emission tomography (PET) myocardial fatty acid metabolism imaging agents and positron emission tomography (PET) 18 The use of F-FDG myocardial glucose imaging agent in the preparation of pharmaceutical agents for combined PET imaging, among which, The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: ； The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: 。 2. The use as described in claim 1, wherein the PET combined imaging is applied to mammals.

3. The use as described in claim 2, wherein, The positron emission tomography myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent was administered to the subjects on the same day. First administer to the subject. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. 18 Imaging was performed approximately one hour after F-FDG injection. Immediately after imaging, a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent was injected, followed by immediate imaging. or Imaging was performed on the subject first using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, followed by administration of... 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed immediately by positron emission tomography (PET) myocardial fatty acid metabolism imaging agent, and then immediately after imaging was completed. 18 F-FDG myocardial glucose imaging agent was used, and imaging was performed approximately one hour after injection. The subjects were required to fast for at least 4 hours before the two imaging agents were administered sequentially.

4. The use as described in claim 3, wherein, When administering the medication to the subjects on the same day, administer it to the subjects first. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging using a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent. The positron 18 The ratio of the injection dose of F-FDG myocardial glucose imaging agent to that of the positron emission tomography myocardial fatty acid metabolism imaging agent is 1:x, and x≥1.

5. The use as described in claim 4, wherein x is 2 to 4.

6. The use as described in claim 3, wherein, When administering the medication to the subjects on the same day, the subjects were first subjected to positron emission tomography (PET) imaging of myocardial fatty acid metabolism, and then administered the medication. 18 Imaging was performed using F-FDG myocardial glucose imaging agent. The positron emission tomography myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injection dose of F-FDG myocardial glucose imaging agent is 1:x, and x≥1.

7. The use as described in claim 6, wherein x is 2 to 4.

8. The use as described in claim 2, wherein, The positron emission tomography myocardial fatty acid metabolism imaging agent and the positron 18 The F-FDG myocardial glucose imaging agent was administered to the subjects on two separate days. Administered to the subject on the first day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent, followed by imaging with a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent on the second day, or... On the first day of administration, the subject was given a positron emission tomography (PET) imaging agent for myocardial fatty acid metabolism, followed by administration on the second day. 18 Imaging was performed using F-FDG myocardial glucose imaging agent; The subjects were required to fast for at least 4 hours on two separate days before receiving the imaging agent.

9. The use as described in claim 2, wherein, The PET images and myocardial perfusion images obtained from the combined PET imaging are used to assess the condition of viable myocardium and scarred myocardium at the site of myocardial infarction.

10. An imaging reagent kit comprising a positron emission tomography (PET) myocardial fatty acid metabolism imaging agent and a positron emission tomography (PET) sensor. 18 F-FDG myocardial glucose imaging agent; The chemical formula of the positron emission tomography (PET) myocardial fatty acid metabolism imaging agent is shown below: ； The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is: 。

Images