CN-122010862-A - Novel PET tracer agent targeting cannabinoid type 2 receptor and preparation method thereof

Abstract

The invention provides a novel PET tracer targeting cannabinoid type 2 receptor and a preparation method thereof.

Inventors

• HE QINGGANG
• JIN CAN
• DU KANG
• CHEN JUNWEI
• CAO XINGHAI
• MIAO LIWEI
• MAO DILONG

Assignees

• 杭州吉蕊科技有限公司

Dates

Publication Date

20260512

Application Date

20241112

Claims (9)

1. 1. A compound, characterized in that, the structural formula of the compound is as follows:
2. 2. a radioactive compound characterized by a compound according to claim 1 as standard wherein fluorine in the group is replaced by a radioisotope 18 F.
3. 3. The radioactive compound of claim 2, wherein the radioactive compound has the formula:
4. 4. Use of a radioactive compound according to claim 2 or 3 for the preparation of a PET imaging agent.
5. 5. The use according to claim 4, wherein the PET imaging agent is a tracer targeting cannabinoid type 1 receptors.
6. 6. The use according to claim 4 or 5, wherein the PET tracer is used for peripheral disease diagnosis.
7. 7. The use according to claim 6, wherein the peripheral diseases include inflammatory bowel disease, pancreatitis, colon cancer, cholangiocarcinoma, pancreatic cancer, etc.
8. 8. The use according to claim 4 or 5, wherein the PET tracer is used to evaluate the effect of an immune drug in the treatment of a cannabinoid type 2 receptor associated disorder.
9. 9. A PET tracer comprising the radioactive compound of claim 3 and a pharmaceutically acceptable carrier.

Description

Novel PET tracer agent targeting cannabinoid type 2 receptor and preparation method thereof Technical Field The invention relates to development and preparation of a lead compound of a novel radioactive drug, and belongs to the technical field of nuclear medicine. In particular to a medicine which can be marked by radionuclide 18 F, a preparation method thereof and the ability of the medicine as a medicine with the ability of targeting cannabinoid type 2 receptor, which is applied to the medical application/research fields of early diagnosis, curative effect monitoring, pathological research, medicine research and development of diseases, in particular peripheral related diseases. Background Endoneuritis is a multi-factor disorder and has close association with a plurality of CNS diseases, so that the understanding of the corresponding neuroinflammation can help people to determine the pathogenesis of the CNS diseases and find out potential treatment and intervention methods. In the study-related data, it was found that cannabinoid receptor 2 (Cannabinoid Receptortype, cb2 r) was considered a very potential target. Because the distribution of CB2R in the CNS is strongly correlated with the distribution of cells such as glial cells, and the expression level of CB2R is significantly up-regulated under neuroinflammatory conditions. CB2R expression in the central nervous system is considered very low, but rather widely occurs on cells and tissues of the immune, reproductive, cardiovascular, gastrointestinal and respiratory systems, and so early studies were named peripheral cannabinoid receptors by some researchers. Recent studies have revealed that CB2R, although not well detected in the normal healthy brain due to low expression in the CNS, is significantly upregulated in a number of pathological conditions, meeting the development conditions of some studies. For example, low levels of CB2 receptors are found in microglial cells, human fetal astrocytes and human brain microvascular endothelial cells. Some neurodegenerative diseases, such as multiple sclerosis, down syndrome and Huntington's disease, also demonstrate considerable enhancement of brain region CB2R expression, and are predominantly manifested on activated microglia. Disorders of CB2R expression also include traumatic brain injury, neuropathic pain, HIV-induced encephalitis, and the like. For this reason, the development of CB2R change studies in CNS diseases such as neuroinflammation, neurodegeneration and glioma with PET would provide more possibilities for the personalized diagnosis and therapeutic monitoring of these diseases. For the many significant changes in CB2R that occur during these diseases/physiological processes, CB2R has gained increasing attention as a CNS target. Positron emission tomography (Positron Emission Tomography, PET) is different from structural imaging technologies such as Magnetic Resonance Imaging (MRI), tomography (CT) and the like, and PET belongs to a functional imaging technology, is a novel imaging technology capable of displaying the activities of substances such as biomolecule metabolism, receptors, nerve mediums and the like on living bodies, and is widely applied to the fields such as diagnosis and differential diagnosis of various diseases, curative effect evaluation, organ function research, new medicine development and the like. Meanwhile, PET imaging has the imaging characteristics of strong specificity, high sensitivity, excellent penetrability and the like. Therefore, when the disease is in a molecular level change stage at early stage and the lesion area of the patient has not been subjected to structural change, and MRI and CT examinations cannot be clearly diagnosed, PET examinations can sensitively find the lesion position, and three-dimensional image information of the patient is provided under a noninvasive condition, so that doctors can conveniently conduct quantitative and qualitative follow-up research and diagnosis, which is incomparable with other image examinations at present. In PET, a core needs to use a PET imaging agent, also called a PET probe, a PET contrast agent, a PET tracer, etc., which is a substance marked by a radionuclide and has a specific recognition and binding of a specific target organ, tissue, enzyme, protein, receptor, etc. after entering the body. After the PET probe enters the body, aggregation is completed in a specific area, and three-dimensional image presentation is completed with the help of signal acquisition equipment and computer imaging software. The most common PET probe is 18-fluoro-deoxyglucose ([ 18 F ] FDG), which is a type of sugar metabolism probe, can specifically image the sugar-consuming part in vivo, and is extremely widely applied to tumor diagnosis and treatment. The research and development of cannabinoid type II receptor drugs and peripheral drug research and development are mainly performed, wherein the research and development proportion of a