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

Abstract

The positron myocardial fatty acid metabolism imaging agent and the positron < 18 > F-FDG myocardial glucose imaging agent are used for PET combined imaging.

Description

Positron-emission myocardial fatty acid metabolism imaging agents and positron 18 Use of F-FDG myocardial glucose imaging agent in combined PET imaging Technical Field

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

[0002] Myocardial viability assessment is a necessary step before coronary revascularization in patients with acute myocardial infarction, old myocardial infarction and complete coronary artery occlusion. Nuclear medicine positron myocardial metabolic imaging is considered to be the most effective method for myocardial viability assessment. However, the current method is to inject blood glucose after adjusting blood glucose. 18 F-FDG myocardial metabolic imaging takes too long (1-4 hours), and often cannot be performed on patients with insulin resistance, and hypoglycemia often occurs during the blood sugar regulation process, resulting in low clinical practicality. 18 F-FDG and positron emission tomography combined myocardial fatty acid metabolism imaging to replace the existing blood glucose control 18 F-FDG myocardial metabolic imaging is used to evaluate viable myocardium and scarred myocardium. This application hopes to propose a new technical solution that can avoid the various problems caused by blood sugar regulation and at the same time provide for viable myocardial assessment.

[0003] Summary of the Invention

[0004] To achieve the above objectives, this application provides:

[0005] 1. Positron myocardial fatty acid metabolism imaging agents and positron 18 Use of a F-FDG myocardial glucose imaging agent for preparing a medicament for PET combined imaging, wherein:

[0006] The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows:

[0007] The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

[0008] 2. The method of claim 1, wherein the PET combined with imaging is applied to mammals.

[0009] 3. The use according to item 2, wherein

[0010] The positron myocardial fatty acid metabolism imaging agent and the positron 18F-FDG myocardial glucose imaging agent was administered to the subjects on the same day.

[0011] When administering, first administer to the subject 18 After imaging with F-FDG myocardial glucose imaging agent, positron myocardial fatty acid metabolism imaging agent is used for imaging. 18 Imaging was performed approximately one hour after F-FDG injection, and positron myocardial fatty acid metabolism imaging agent was injected immediately after imaging was completed.

[0012] or

[0013] First, the subjects were given positron-emission myocardial fatty acid metabolism imaging agents for imaging and then given 18 Imaging was performed with F-FDG myocardial glucose imaging agent, and imaging was performed immediately after the injection of positron myocardial fatty acid metabolism imaging agent. 18 F-FDG myocardial glucose imaging agent, imaging is performed nearly one hour after injection,

[0014] The subject needs to fast for at least 4 hours before sequentially administering the two imaging agents.

[0015] 4. The use according to item 3, wherein when administered to a subject on the same day, the subject is first administered 18 F-FDG myocardial glucose imaging agent is used for imaging, and then a positron myocardial fatty acid metabolism imaging agent is administered to the subject for imaging,

[0016] The positron 18 The ratio of the injection dose (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.

[0017] 5. The use according to item 4, wherein x is 2 to 4.

[0018] 6. The use according to item 3, wherein, when administered to a subject on the same day, the subject is first administered a positron myocardial fatty acid metabolism imaging agent for imaging, and then the subject is administered 18 F-FDG myocardial glucose imaging agent was used for imaging.

[0019] The positron myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injected dose of F-FDG myocardial glucose imaging agent (unit: mCi or MBq) is 1:x, and x ≥ 1.

[0020] 7. The use according to item 6, wherein x is 2 to 4.

[0021] 8. The use according to item 2, wherein the positron myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent is administered to the subject on two separate days.

[0022] Administer to the subject on the first day 18 F-FDG myocardial glucose imaging and then positron emission tomography myocardial fatty acid metabolism imaging on the second day, or

[0023] During administration, the subjects were administered a positron-emission myocardial fatty acid metabolism imaging agent on the first day for imaging, and then on the second day, the subjects were administered 18 Imaging was performed with F-FDG myocardial glucose imaging agent;

[0024] The subject needs to fast for at least 4 hours before administering the imaging agent on two separate days.

[0025] 9. The use as described in item 2, wherein the PET image of the PET combined imaging is used together with the myocardial perfusion image to evaluate the viable myocardium and scar myocardium at the site of myocardial infarction, and the myocardial perfusion image is obtained from SPECT or PET myocardial perfusion imaging.

[0026] 10. An imaging agent kit comprising a positron myocardial fatty acid metabolism imaging agent and a positron 18 F-FDG myocardial glucose imaging agent;

[0027] The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows:

[0028] The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

[0029] Beneficial technical effects achieved by the technical solution of this application

[0030] Adopting the scheme of this application, you can avoid adjusting blood sugar 18 The low efficiency of F-FDG myocardial metabolic imaging, poor image quality in patients with insulin resistance, and hypoglycemia during blood glucose regulation will be addressed, thereby improving the clinical practicality of nuclear medicine myocardial metabolic imaging, allowing more patients with myocardial infarction to obtain a complete assessment of myocardial viability before undergoing revascularization, and then decide on the necessity of major surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG1a is a SPECT myocardial perfusion image according to Example 1, and FIG1b-1c are 18 Combined imaging results of F-FDG and XTR003 PET.

[0032] FIG2a is a SPECT myocardial perfusion image according to Example 2, and FIG2b-2c are 18 Combined imaging results of F-FDG and XTR003 PET.

[0033] Figures 3a-3b are diagrams of the comparative example 1. 18 Combined imaging results of F-FDG and XTR003 PET.

[0034] Figures 4a-4b show the XTR003 and 18 F-FDG PET combined imaging results.

[0035] Figures 5a-5b show the XTR003 and 18 F-FDG PET combined imaging results.

[0036] Figures 6a-6b are diagrams of a method according to Example 4. 18 Combined imaging results of F-FDG and XTR003 PET.

[0037] Figures 7a and 7b are diagrams of the comparative example 3. 18 F-FDG and XTR003 PET imaging results, respectively.

[0038] Figures 8a-8b are diagrams of the comparative example 4. 18 Combined imaging results of F-FDG and XTR003 PET.

[0039] Figures 9a-9b show the XTR003 and 18 F-FDG PET combined imaging results. DETAILED DESCRIPTION

[0040] Specific embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. Although specific embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0041] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" is an open term, so it should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present invention, but the description is based on the general principles of the specification and is not intended to limit the scope of the invention. The scope of protection of the present invention shall be as defined in the attached claims.

[0042] As used herein, "substantially free" with respect to a particular component is used herein to mean that the particular component is not purposefully formulated 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 any unintentional contamination of the composition is less than 0.05%, preferably less than 0.01%. Most preferred are compositions wherein the amount of the particular component is undetectable by standard analytical methods.

[0043] 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 than one.

[0044] The term "or" is used in the claims to mean "and / or" unless explicitly stated to refer only to alternatives or the alternatives are mutually exclusive, although the content of this application supports a definition referring only to alternatives and "and / or." As used herein, "another" can mean at least a second or more.

[0045] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for the device, the method employed to determine the value, or the variation that exists between study subjects.

[0046] In the first aspect, the present application provides a positron myocardial fatty acid metabolism imaging agent and a positron 18 The invention relates to the use of F-FDG myocardial glucose imaging agent for preparing a medicament for PET combined imaging.

[0047] In one 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, wherein,

[0048] The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows:

[0049] In the context of this specification, the compound is referred to as XTR003.

[0050] The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

[0051] In the context of this specification, the positron emission tomography myocardial metabolic imaging method is an effective method for evaluating viable myocardium. A common practice is to inject 18 F-FDG is used for myocardial metabolic imaging. The problem is that myocardial metabolic imaging takes too long (1-4 hours), and often cannot be performed on patients with insulin resistance and often suffers from hypoglycemia during the blood sugar regulation process, resulting in low clinical practicality. This application creatively allows subjects to undergo myocardial metabolic imaging on an empty stomach. 18 F-FDG and positron emission tomography combined myocardial fatty acid metabolism imaging to replace the existing blood glucose control 18 F-FDG myocardial metabolic imaging. Here, myocardial energy metabolism includes glucose metabolism and fatty acid metabolism, which regulates blood sugar. 18 F-FDG myocardial metabolic imaging converts myocardial fatty acid metabolism into single glucose metabolism to present the energy metabolism of the whole myocardium by regulating blood sugar. 18 Combined imaging of F-FDG and positron myocardial fatty acid metabolism can simultaneously display the total energy metabolism of the myocardium through (glucose metabolism + fatty acid metabolism).

[0052] In one embodiment, the aforementioned use is provided, wherein the PET combined with imaging is applied to a mammal.

[0053] In another embodiment, the aforementioned use is provided, wherein,

[0054] The positron 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.

[0055] When administering, first administer to the subject 18 After imaging with F-FDG myocardial glucose imaging agent, positron myocardial fatty acid metabolism imaging agent is used for imaging. 18 Imaging was performed approximately one hour after F-FDG injection, and positron-emission myocardial fatty acid metabolism imaging agent was injected immediately after imaging was completed, and imaging was performed immediately.

[0056] In another embodiment, the above-mentioned use is provided, wherein the positron myocardial fatty acid metabolism imaging agent is combined with the positron 18 F-FDG myocardial glucose imaging agent was administered to the subjects on the same day.

[0057] First, the subjects were given positron-emission myocardial fatty acid metabolism imaging agents for imaging and then given 18 Imaging was performed with F-FDG myocardial glucose imaging agent, and imaging was performed immediately after the injection of positron myocardial fatty acid metabolism imaging agent. 18 F-FDG myocardial glucose imaging agent was injected approximately one hour later.

[0058] The subject needs to fast for at least 4 hours before sequentially administering the two imaging agents.

[0059] In the context of this specification, "administration" can refer to various methods of drug ingestion, the purpose of which is to allow the drug to enter the human blood circulation and reach sufficient concentration in a specific organ or site before being metabolized and eliminated to exert an imaging effect. "Administration" can include oral administration or intravenous injection. When administered orally, the imaging agent can be in the form of tablets, powders, or oral solutions; when administered intravenously, the imaging agent can be in the form of an injectable solution.

[0060] In another embodiment, the above-mentioned use is provided, wherein, when administered to a subject on the same day, the subject is first administered 18 F-FDG myocardial glucose imaging agent is used for imaging, and then a positron myocardial fatty acid metabolism imaging agent is administered to the subject for imaging,

[0061] The positron 18 The ratio of the injected doses (unit: mCi or MBq) of the F-FDG myocardial glucose imaging agent to the positron-emission myocardial fatty acid metabolism imaging agent is 1:x, where x ≥ 1; preferably 1:2 to 4, and most preferably 1:3. As examples, 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.

[0062] In the context of this specification, the value of x can be infinite, but in actual use, values ​​of x = 2 to 4 are most often used. This is because this range achieves a relatively ideal performance-cost ratio. When x is greater than 4, the imaging effect gradually improves, but the degree of increase in effect is not linearly related to the injected dose.

[0063] 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.

[0064] In one embodiment, the above-mentioned use is provided, wherein, when administered to a subject on the same day, the subject is first administered with a positron myocardial fatty acid metabolism imaging agent for imaging, and then administered to the subject 18F-FDG myocardial glucose imaging agent was used for imaging.

[0065] The positron myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injected dose of F-FDG myocardial glucose imaging agent (unit: mCi or MBq) is 1:x, where x ≥ 1; preferably 1:2 to 4; and most preferably 1:3. As examples, 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.

[0066] In the context of this specification, the value of x can be infinite, but in actual use, values ​​of x = 2 to 4 are most often used. This is because this range achieves a relatively ideal performance-cost ratio. When x is greater than 4, the imaging effect gradually improves, but the degree of increase in effect is not linearly related to the injected dose.

[0067] In the context of this specification, the value of x must be greater than 1. 18 F-FDG and XTR003 are both 18 For F-labeled PET imaging agents, when the value of x is less than 1, the myocardial uptake of the first injected agent will interfere with the signal of the second injected agent, affecting the accuracy of the latter PET imaging.

[0068] In another embodiment, the above-mentioned use is provided, wherein the positron myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent is administered to the subject on two separate days.

[0069] Administer to the subject on the first day 18 F-FDG myocardial glucose imaging agent was used for imaging, and then on the second day, positron myocardial fatty acid metabolism imaging agent was used for imaging.

[0070] The subject needs to fast for at least 4 hours before administering the imaging agent on two separate days.

[0071] In another embodiment, the above-mentioned use is provided, wherein the positron myocardial fatty acid metabolism imaging agent and the positron 18 F-FDG myocardial glucose imaging agent is administered to the subject on two separate days.

[0072] During administration, the subjects were administered a positron-emission myocardial fatty acid metabolism imaging agent on the first day for imaging, and then on the second day, the subjects were administered 18 Imaging was performed with F-FDG myocardial glucose imaging agent;

[0073] The subject needs to fast for at least 4 hours before administering the imaging agent on two separate days.

[0074] In the context of this specification, the administration of the imaging agent twice a day and separately on two days are also referred to as "one-day method" and "two-day method", respectively. The terms "one-day method" and "two-day method" are general concepts well known in the field of imaging agents.

[0075] In another specific embodiment, the above-mentioned use is provided, wherein the PET image of the PET combined imaging is used in combination with the myocardial perfusion image to evaluate the viable myocardium and scar myocardium at the site of myocardial infarction, and the myocardial perfusion image is obtained from SPECT or PET myocardial perfusion imaging.

[0076] In the context of this specification, PET is the abbreviation of "Positron Emission Computed Tomography"; it is a relatively advanced clinical examination imaging technology in the field of nuclear medicine. The general method of PET is to label a substance, generally a substance essential for biological metabolism, such as glucose, protein, nucleic acid, fatty acid, with a short-lived radionuclide (such as 18 F. 11 C, etc.), after being injected into the human body, the accumulation of this substance during metabolism reflects the state of life metabolic activities, thereby achieving the purpose of diagnosis. The substance mainly used in various hospitals is fluorodeoxyglucose, abbreviated as FDG. Its mechanism is that different tissues in the human body have different metabolic states. In highly metabolic malignant tumor tissues, glucose metabolism is vigorous and accumulates more. These characteristics can be reflected in the image, so that the lesions can be diagnosed and analyzed. In the context of this manual, "myocardial perfusion imaging" is a non-invasive test for heart disease. It was first used in the 1970s. After nearly 40 years of development, its great diagnostic value has been widely accepted worldwide, and it has become an important imaging method for diagnosing coronary heart disease, evaluating therapeutic effects, and judging prognosis. Myocardial perfusion imaging includes single photon emitter 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-methoxyisocyanate (Tc-99m-MIBI), and technetium-99m-tetrofosmin.

[0077] In a second aspect, the present application provides an imaging agent kit.

[0078] In one embodiment, an imaging agent kit is provided, which includes a positron myocardial fatty acid metabolism imaging agent and a positron 18 F-FDG myocardial glucose imaging agent;

[0079] The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows:

[0080] The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

[0081] Based on the above use, the kit provides an amount sufficient for at least a single use for 75 kg of humans, wherein the positron myocardial fatty acid metabolism imaging agent is combined with the 18 The injection dose of F-FDG myocardial glucose imaging agent (unit: mCi or MBq) is in the ratio of 1:2-5, and the absolute injection dose is, for example, 1 mCi:2-5 mCi; or the positron 18 The ratio of the injection dose (unit: mCi or MBq) of the F-FDG myocardial glucose imaging agent to the positron myocardial fatty acid metabolism imaging agent is 1:2-5; the absolute injection dose is, for example, 1 mCi:2-5 mCi.

[0082] Examples

[0083] Example 1

[0084] Each experiment used a Bama miniature pig of about one year old, 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 myocardium. Four weeks later, as a comparative experiment, 99mTc-Sestamibi SPECT myocardial perfusion imaging (this imaging is the gold standard for evaluating viable myocardium and scar myocardium in the myocardial infarction site and is used to compare the PET imaging effect in this example) was performed in the morning; in the afternoon, a one-day method was used. 18 F-FDG and XTR003 PET combined imaging (at least 2 hours apart from the SPECT in the morning, and fasting should be maintained during the interval), first 18 After F-FDG PET imaging, XTR003 PET imaging was performed. The injection doses of the above two drugs were 1mCi and 2.5mCi, respectively. 18 F-FDG was injected 1 hour after XTR003 injection, followed by PET imaging immediately.

[0085] SPECT myocardial perfusion images, 18 The combined imaging results of F-FDG and XTR003 PET are shown in Figures 1a-1c. Image interpretation:

[0086] Figure 1a. 99mTc-Sestamibi myocardial perfusion image: A small area of ​​decreased myocardial perfusion from the apical segment to the mid-segment of the anterior wall represents the area of ​​myocardial infarction (as indicated by the dotted line).

[0087] Figure 1b. Fasting 18 F-FDG myocardial metabolic image: corresponding to the myocardial infarction area 18 The low F-FDG uptake indicates that the myocardial infarction is in a low glucose metabolism state (as shown in the dotted box).

[0088] Figure 1c. Fasting XTR003 myocardial metabolism image: There is still moderate XTR003 uptake in the corresponding myocardial infarction area, indicating that the myocardial infarction is in a moderate fatty acid metabolism state (as shown in the dotted box range); the comparison of Figure 1a, Figure 1b and Figure 1c shows that there is still viable myocardium in the small area of ​​myocardial infarction from the apical segment to the middle segment of the anterior wall.

[0089] Example 2

[0090] Each experiment used a Bama miniature pig of about one year old, 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 on the left anterior descending coronary artery, 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; in the afternoon, a one-day method was used. 18 F-FDG and XTR003 PET combined imaging, first 18 After F-FDG PET imaging, XTR003 PET imaging was performed. The injection doses of the above two drugs were 1mCi and 3.1mCi respectively. 18 F-FDG was injected 1 hour after XTR003 injection, followed by PET imaging immediately.

[0091] SPECT myocardial perfusion images, 18 The combined imaging results of F-FDG and XTR003 PET are shown in Figures 2a-2c. Image interpretation:

[0092] Figure 2a. 99mTc-Sestamibi myocardial perfusion image: A large area of ​​decreased myocardial perfusion from the apex to the basal segment represents the area of ​​myocardial infarction (as shown in the box);

[0093] Figure 2b. Fasting 18 F-FDG myocardial metabolic image: no 18 F-FDG uptake indicates that the myocardial infarction is in a state of no glucose metabolism (as shown in the boxed area);

[0094] Figure 2c. Fasting XTR003 myocardial metabolism image: There is no XTR003 uptake in the corresponding myocardial infarction area, indicating that the myocardial infarction is in a state of no fatty acid metabolism (as shown in the boxed area);

[0095] Comparison of Figures 2a, 2b, and 2c shows that the large-scale myocardial infarction area from the apical segment to the basal segment of the anterior wall is myocardial necrosis, and scar myocardium has formed.

[0096] Comparative Example 1 Study: First 18 Imaging effect of XTR003 PET imaging (injection ratio 1:x, and x is less than 1) after F-FDG PET imaging

[0097] The disease animal model was constructed according to the description of Example 1, and the "one-day method" was implemented after myocardial perfusion imaging. 18 F-FDG PET and XTR003 PET combined imaging", in which 18 F-FDG was injected with XTR003 1 hour after injection, followed by PET imaging immediately afterwards; the only difference between this comparative example and Example 1 was that the injection doses of the two agents were 1 mCi and 0.25 mCi, respectively; 18 The combined imaging results of F-FDG and XTR003 PET (also taking the second experiment of three experiments as an example) are shown in Figures 3a-3b.

[0098] Figure 3a. Fasting 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal.

[0099] Figure 3b. Fasting XTR003 myocardial metabolic image. Compared with Figure 1c, the image noise is too high and imaging fails because the XTR003 injection dose ratio is too low.

[0100] Example 3 Study: First XTR003 PET imaging followed by 18 F-FDG PET imaging has equally good imaging effects.

[0101] The disease animal model was constructed according to the description of Example 1. The only difference from Example 1 was the imaging sequence. Specifically, XTR003 PET imaging was performed first, followed by 18 For F-FDG PET imaging, the injection doses of the above two agents were 1mCi and 3mCi, respectively; XTR003 and 18 The results of F-FDG PET combined imaging are shown in Figures 4a-4b. In the figure:

[0102] Figure 4a. Fasting XTR003 myocardial metabolic image. Compared with Figure 1c, the image quality is normal.

[0103] Figure 4b. Fasting 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal.

[0104] Comparative Example 2 Study: First XTR003 PET imaging followed by 18Imaging effect of F-FDG PET imaging (injection ratio 1:x, and x is less than 1)

[0105] The disease animal model was constructed according to the description of Example 3, and after the myocardial perfusion phenomenon, the "one-day method XTR003 PET and 18 F-FDG PET combined imaging", in which XTR003 was injected 1 hour after injection 18 F-FDG, followed by PET imaging immediately; the difference between this comparative example and Example 3 is that the injection doses of the above two agents are 1mCi and 0.25mCi respectively; XTR003 and 18 The results of F-FDG PET combined imaging are shown in Figures 5a-5b. In the figure:

[0106] Figure 5a. Fasting XTR003 myocardial metabolic image. Compared with Figure 4a, the image quality is normal.

[0107] Figure 5b. Fasting 18 F-FDG myocardial metabolic images, compared with Figure 4b, 18 The F-FDG injection dose ratio is too low, resulting in excessive image noise and imaging failure.

[0108] Example 4 Study: Imaging Effect of the "Two-Day Method"

[0109] The disease animal model was constructed according to the description of Example 1. The only difference from Example 1 was that the "two-day method" was implemented after the myocardial perfusion phenomenon. 18 F-FDG PET and XTR003 PET combined imaging” rather than “one-day method”. 18 The combined imaging results of F-FDG and XTR003 PET are shown in Figures 6a-6b.

[0110] In the picture:

[0111] Figure 6a. Fasting 18 F-FDG myocardial metabolic image. Compared with Figure 1b, the image quality is normal.

[0112] Figure 6b. Fasting XTR003 myocardial metabolic image. Compared with Figure 1c, the image quality is normal.

[0113] Comparative Example 3 Study on the applicability of "using a single imaging agent without combination"

[0114] Each experiment used a Bama miniature pig of about one year old, and the experiment was repeated three times; taking the second experiment of the three experiments as an example: the piglet weighed about 10 kg, and the two injections were imaged separately rather than jointly. 18 The results of F-FDG and XTR003 PET imaging are shown in Figures 7a and 7b, respectively.

[0115] Figure 7a. Fasting 18 F-FDG myocardial metabolic images, compared with Figure 1b, are not visible.

[0116] Figure 7b. Fasting XTR003 myocardial metabolic image. Compared with Figure 1c, the imaging is normal.

[0117] Since the glucose metabolism rate of normal myocardium is low (10%-30%), and the fatty acid metabolism rate is high (60%-90%), 18 F-FDG showed almost no image, while XTR003 showed normal image.

[0118] Comparative Example 4 Study: First 18 Imaging effect of XTR003 PET imaging (injection ratio 1:x, and x greater than 4) after F-FDG PET imaging

[0119] The disease animal model was constructed according to the description of Example 1, and the "one-day method" was implemented after myocardial perfusion imaging. 18 F-FDG PET and XTR003 PET combined imaging", in which 18 F-FDG was injected with XTR003 1 hour after injection, followed by PET imaging immediately afterwards; the only difference between this comparative example and Example 1 was that the injection doses of the two agents were 1 mCi and 1, 2, 3, 4, and 6 mCi, respectively; 18 The combined imaging results of F-FDG and XTR003 PET (also taking the second experiment of three repeated experiments as an example) are shown in Figures 8a-9b.

[0120] Figure 8a. is as 18 Changes in image quality with varying ratios of F-FDG PET and XTR003 PET.

[0121] Figure 8b. is as 18 Actual images of the changing ratio of F-FDG PET and XTR003 PET.

[0122] Comparative Example 5 Study: First XTR003 PET imaging followed by 18 Imaging effect of F-FDG PET imaging (injection ratio 1:x, and x greater than 4)

[0123] The disease animal model was constructed according to the description of Example 3, and after the myocardial perfusion phenomenon, the "one-day method XTR003 PET and 18 F-FDG PET combined imaging", in which XTR003 was injected 1 hour after injection 18F-FDG, followed by PET imaging immediately; the difference between this comparative example and Example 3 is that the injection doses of the above two agents are 1mCi and 1, 2, 3, 4, 6mCi respectively; XTR003 PET and 18 The results of F-FDG combined imaging are shown in Figures 9a-9b. In the figure:

[0124] Figure 9a. is the XTR003 PET and 18 Changes in image quality with varying ratios of the two F-FDG PET agents.

[0125] Figure 9b shows the XTR003 PET and 18 Actual images of the changing ratio of the two drugs using F-FDG PET.

[0126] It should be noted that when using the "one-day method" for imaging, the greater the amount of last-dose contrast agent used, the better the imaging effect. However, increasing the injection-dose ratio to >4 does not further improve image quality. On the contrary, excessive doses can significantly increase contrast agent costs and increase radiation risk to patients. Experimental studies have shown that ideal imaging results are achieved when the ratio of first-dose contrast agent to last-dose contrast agent is within the range of 1:2 to 4.

[0127] Although the embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to the above-mentioned specific embodiments and application fields. The above-mentioned specific embodiments are merely illustrative and instructive, and are not restrictive. A person skilled in the art, guided by this specification and without departing from the scope of protection of the claims of the present invention, may also devise various forms, all of which fall within the scope of protection of the present invention.

Claims

1. Positron myocardial fatty acid metabolism imaging agents and positron 18 Use of F-FDG myocardial glucose imaging agent for preparing a medicament for PET combined imaging, wherein: The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows: The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

2. The use according to claim 1, wherein the PET combined imaging is applied to mammals.

3. The use according to claim 2, wherein The positron 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. When administering, first administer to the subject 18 After F-FDG myocardial glucose imaging agent is used for imaging, positron myocardial fatty acid metabolism imaging agent is used for imaging. 18 Imaging was performed nearly one hour after F-FDG injection, and positron myocardial fatty acid metabolism imaging agent was injected immediately after imaging was completed and imaging was performed immediately. or The subjects were first given a positron-emission myocardial fatty acid metabolism imaging agent for imaging and then given 18 Imaging was performed with F-FDG myocardial glucose imaging agent, and imaging was performed immediately after injection of positron myocardial fatty acid metabolism imaging agent. 18 F-FDG myocardial glucose imaging agent, imaging is performed nearly one hour after injection, The subject needs to fast for at least 4 hours before sequentially administering the two imaging agents.

4. The use according to claim 3, wherein When administered to a subject on the same day, the subject is first administered 18 F-FDG myocardial glucose imaging agent is used for imaging, and then a positron myocardial fatty acid metabolism imaging agent is administered to the subject for imaging, The positron 18 The ratio of the injection dose of the F-FDG myocardial glucose imaging agent to the injection dose of 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. The use according to claim 3, wherein When administered to a subject on the same day, the subject is first administered a positron myocardial fatty acid metabolism imaging agent for imaging, and then the subject is administered 18 F-FDG myocardial glucose imaging agent was used for imaging. The positron myocardial fatty acid metabolism imaging agent and the 18 The ratio of the injected dose of F-FDG myocardial glucose imaging agent is 1:x, and x≥1.

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

8. The use according to claim 2, wherein 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. When administered, the subjects were administered on the first day. 18 F-FDG myocardial glucose imaging agent, and then on the second day, the subjects are given positron-emitting myocardial fatty acid metabolism imaging agent for imaging, or During administration, the subjects were administered a positron-emission myocardial fatty acid metabolism imaging agent on the first day for imaging, and then the subjects were administered 18 Imaging was performed with F-FDG myocardial glucose imaging agent; The subject needs to fast for at least 4 hours before administering the above imaging agent on two days.

9. The use according to claim 2, wherein The PET image and the myocardial perfusion image of the PET combined imaging are used together to evaluate the viable myocardium and scarred myocardium at the site of myocardial infarction. The myocardial perfusion image is obtained from SPECT or PET myocardial perfusion imaging.

10. An imaging agent kit comprising a positron myocardial fatty acid metabolism imaging agent and a positron 18 F-FDG myocardial glucose imaging agent; The chemical formula of the positron myocardial fatty acid metabolism imaging agent is as follows: The positron 18 The chemical formula of F-FDG myocardial glucose imaging agent is:

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