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CN-121974975-A - PET and NIR bimodal diagnosis and treatment integrated molecular probe, preparation and application

CN121974975ACN 121974975 ACN121974975 ACN 121974975ACN-121974975-A

Abstract

The invention relates to a PET and NIR bimodal diagnosis and treatment integrated molecular probe, and preparation and application thereof, and belongs to the technical field of medical imaging. The PET/NIR probe is a PET/NIR bimodal diagnosis and treatment integrated molecular probe targeting the CD206 receptor on the surface of M2 tumor-associated macrophages, and has a structure shown in a formula I. The probe has the characteristics of rapid tumor imaging, long-time retention in tumors and rapid removal of normal organs. The probe can be used for preoperative PET/CT imaging, systematic diagnosis of focus, guidance of making an operation route, accurate positioning of tumor boundaries by intraoperative fluorescence imaging, and improvement of postoperative curative effect.

Inventors

  • ZHU JINTAO
  • XU HANBIN
  • LIU YIJING
  • QIN JINYING
  • TANG KUN
  • LI JIANGUO

Assignees

  • 华中科技大学
  • 华中科技大学同济医学院附属同济医院
  • 中国辐射防护研究院

Dates

Publication Date
20260505
Application Date
20260128

Claims (10)

  1. 1. The PET/NIR bimodal diagnosis and treatment integrated molecular probe is characterized in that the structure of the probe is shown as a formula I: ; I is a kind of Wherein R is a nuclide chelating group, and F is a fluorescent group.
  2. 2. The PET/NIR bimodal diagnostic integrated molecular probe of claim 1, wherein the nuclide chelating group is DOTA or NOTA, having the structural formula: 。
  3. 3. The PET/NIR bimodal diagnostic integrated molecular probe of claim 1, wherein said fluorophore is a near infrared fluorophore.
  4. 4. The PET/NIR bimodal diagnostic integrated molecular probe of claim 3, wherein the fluorescent group is ICG, cy7, cy7.5, IR780, IR800, IR-820 or FD 1080.
  5. 5. The method for preparing the PET/NIR bimodal diagnosis and treatment integrated molecular probe according to any one of claims 1 to 4, comprising the steps of: (1) Performing amino coupling reaction on fluorescent molecules and a compound N-alpha-fluorenylmethoxycarbonyl-N-epsilon-t-butoxycarbonyl-L-lysine, removing 9-fluorenylmethoxycarbonyl, and purifying by a silica gel column to obtain a compound 1; (2) Performing amino coupling reaction on the compound 1 and azidoacetic acid, removing tert-butoxycarbonyl, and purifying by a silica gel column to obtain a compound 2; (3) Carrying out coupling reaction on the compound 2 and a nuclide chelating agent, and dialyzing to obtain a compound 3; (4) Click chemistry reaction is carried out on the compound 3 and M2pep polypeptide modified with DBCO, the amino acid of the M2pep polypeptide is shown as SEQ ID NO. 1, and the structural formula of the DBCO is And purifying by high performance liquid chromatography to obtain the PET/NIR bimodal diagnosis and treatment integrated molecular probe.
  6. 6. Use of a PET/NIR bimodal diagnostic integral molecular probe according to any one of claims 1 to 4 for the preparation of a tumor imaging formulation.
  7. 7. The use according to claim 6, wherein the imaging is PET imaging and/or fluorescence imaging.
  8. 8. The use according to claim 6 or 7, wherein the molecular probe is labeled with a radionuclide and then used for imaging.
  9. 9. The use according to claim 8, wherein the radionuclide is a diagnostic radionuclide or a therapeutic radionuclide; Preferably, the diagnostic radionuclide is 68 Ga、 64 Cu、 18 F、 86 Y、 89 Zr or 111 In and the therapeutic radionuclide is 177 Lu、 161 Tb、 211 At、 153 Sm、 186 Re、 188 Re、 67 Cu、 212 Pb、 225 Ac、 213 Bi、 212 Bi or 212 Pb.
  10. 10. The use according to claim 6 or 7, wherein the tumour is a bladder cancer tumour, a breast cancer tumour or glioblastoma; preferably, the tumor is a bladder cancer tumor.

Description

PET and NIR bimodal diagnosis and treatment integrated molecular probe, preparation and application Technical Field The invention relates to the technical field of medical imaging, in particular to a PET and NIR bimodal diagnosis and treatment integrated molecular probe, and preparation and application thereof. Background Currently, the clinical treatment of bladder cancer is primarily surgical excision, supplemented with chemotherapy, radiation therapy and immunotherapy. The positive and missed detection of the incisional edge in the operation is one of the 'murder' of the high recurrence of bladder cancer, which causes great psychological and economic burden for patients. Therefore, the primary focus and metastasis of the bladder cancer can be discovered early, comprehensively, accurately and dynamically, and the method has important significance for guiding clinical accurate staging, judging prognosis, selecting treatment scheme and judging curative effect. Compared with targeting tumor cells, the targeting quantity is more, the cell uptake capacity is higher, and tumor-associated macrophages (TAMs) distributed near tumor blood vessels have advantages. Wherein, the M2 type TAMs are closely related to the occurrence and development processes of cancers, and the design of molecular probes targeting the M2 type TAMs is a diagnosis and treatment mode with great development prospects. The CD206 receptor is a biomarker for TAMs of type M2, is highly expressed at lesions and is highly correlated with malignancy of bladder cancer, and can be used as a target for probe design. The limitations of a single imaging modality limit physicians to formulate personalized and accurate clinical protocols for patients. Therefore, the advantages of different imaging technologies are integrated, a multi-mode clinical diagnosis and treatment mode is developed, the limitation of a single mode is overcome, and the accuracy and the sensitivity of diagnosis are improved. Disclosure of Invention The invention provides a PET/NIR bimodal diagnosis and treatment integrated molecular probe for tumors, which has the characteristic of dynamic change of a visible focus, can realize preoperative PET imaging, simultaneously provides accurate imaging reference for intraoperative tumor cutting edge evaluation, can perform fluorescence operation navigation in the operation and combines preoperative PET imaging to realize accurate intraoperative tracing of tumor boundaries, and can be used for radioactive treatment of inoperable parts in multiple metastases after chelating therapeutic radionuclides. The probe can improve the accuracy and the sensitivity of living body imaging, thereby solving the technical problems of single mode limitation, low accuracy and sensitivity of tumor imaging in the prior art. According to a first aspect of the invention, there is provided a PET/NIR bimodal diagnosis and treatment integrated molecular probe, the structure of the probe is shown in formula I: ; I is a kind of Wherein R is a nuclide chelating group, and F is a fluorescent group. Preferably, the nuclide chelating group is DOTA or NOTA, having the structural formula: 。 Preferably, the fluorophore is a near infrared fluorophore. Preferably, the fluorescent group is a group formed by ICG, cy7, cy7.5, IR780, IR800, IR-820 or FD 1080. According to another aspect of the invention, a preparation method of the PET/NIR bimodal diagnosis and treatment integrated molecular probe is provided, which comprises the following steps: (1) Performing amino coupling reaction on fluorescent molecules and a compound N-alpha-fluorenylmethoxycarbonyl-N-epsilon-t-butoxycarbonyl-L-lysine, removing 9-fluorenylmethoxycarbonyl, and purifying by a silica gel column to obtain a compound 1; (2) Performing amino coupling reaction on the compound 1 and azidoacetic acid, removing tert-butoxycarbonyl, and purifying by a silica gel column to obtain a compound 2; (3) Carrying out coupling reaction on the compound 2 and a nuclide chelating agent, and dialyzing to obtain a compound 3; (4) Click chemistry reaction is carried out on the compound 3 and M2pep polypeptide modified with DBCO, the amino acid of the M2pep polypeptide is shown as SEQ ID NO. 1, and the structural formula of the DBCO is And purifying by high performance liquid chromatography to obtain the PET/NIR bimodal diagnosis and treatment integrated molecular probe. According to another aspect of the invention, the application of the PET/NIR bimodal diagnosis and treatment integrated molecular probe in preparing tumor imaging preparations is provided. Preferably, the imaging is PET imaging and/or fluorescence imaging. Preferably, the molecular probe is labeled with a radionuclide and then used for imaging; Preferably, the radionuclide is a diagnostic radionuclide or a therapeutic radionuclide; Preferably, the diagnostic radionuclide is 68Ga、64Cu、18F、86Y、89 Zr or 111 In and the therapeutic radionuclide is 177Lu、161Tb、211At、153Sm、186