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Clinical single-tube fluorine-18 multifunctional modular equipment and radiopharmaceutical synthesis process

A multifunctional, clinical technology, applied in radioactive carriers, chemical/physical processes, chemical/physical/physicochemical processes, etc., can solve problems such as ineffective integration, disconnection, and decreased synthesis efficiency, and achieve reduction of additional radiation dose, Eliminate the interference of impurities and avoid the effect of solvent conversion

Active Publication Date: 2022-05-20
派特(北京)科技有限公司
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AI Technical Summary

Problems solved by technology

[0004] 1. Based on 18 F-FDG synthesis, the module that assists the HPLC separation system, adopts a separate nucleophilic synthesis and purification system, which cannot effectively integrate the whole process of synthesis, separate operations in the operation, and there is a disconnection phenomenon, and new drugs cannot be developed independently in the later stage
[0005] 2. The powerful All-In-One module synthesizes different nuclides on the same module, and there is a problem of mutual contamination of nuclides, which does not meet the GCP requirements for drug synthesis; at the same time, there is a phenomenon of valve waste due to multiple valve combinations
[0007] 4. All the above modules measure the radioactivity of the product outlet pipeline during HPLC separation, and there is no display for the distribution and residue of radioactivity on the HPLC column, and it is impossible to warn the radioactive peak of the product
Especially when there are multiple side reactions, when a large radioactivity peak is detected in the time-activity curve of the product (such as figure 1 As shown, at Rt=10.2min, a radioactivity peak occurs), it is impossible to judge whether it is a product or an impurity
[0008] At the same time, the volume of the product cannot be calculated according to the radioactivity peak, and there is no way to correctly adjust the pH of the final product and estimate the radiochemical purity of the product, which is usually done manually in the later stage
[0009] 5. After the final product is sterilized by a sterile filter membrane, due to the certain lipophilicity of the product, more radioactivity remains on the sterile filter membrane, generally around 5%, and some are as high as 20%, resulting in a decrease in synthesis efficiency At the same time, in order to verify the integrity of the sterile filter membrane after use, it is necessary to take the sterile filter membrane out of the hot chamber immediately after use to measure whether it is complete, and this operation causes additional radiation doses to the staff

Method used

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  • Clinical single-tube fluorine-18 multifunctional modular equipment and radiopharmaceutical synthesis process
  • Clinical single-tube fluorine-18 multifunctional modular equipment and radiopharmaceutical synthesis process
  • Clinical single-tube fluorine-18 multifunctional modular equipment and radiopharmaceutical synthesis process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 118

[0048] Example 1. 18 Synthesis of F-DCFPyL

[0049] Such as image 3 As shown, the reagents were installed in the following bottles before synthesis and installed on the module:

[0050] B1: 1mL acetonitrile solution containing TBA; B2: 2mL acetonitrile; B3: 5mg precursor dissolved in 0.5mL acetonitrile; B4: 0.5ml 50% phosphoric acid (V / V); B5: 7mL HPLC mobile phase; B6: 10mL 0.5mol / L NaHCO 3 .

[0051] will 2200mCi 18 F ions are transmitted from the accelerator to the QMA column, start the automatic program, and run automatically under the control of the computer: use the acetonitrile solution containing TBA in the B1 bottle to rinse the QMA column into the reaction tube, heat, ventilate and azeotrope to remove water with acetonitrile, and then Add acetonitrile in bottle B2 to remove water repeatedly, cool to 45°C, add precursor in bottle B3, nucleophilic reaction at 50°C for 5 minutes, then add phosphoric acid in bottle B4, hydrolyze at 50°C for 10 minutes, add HPLC in...

Embodiment 218F-7

[0054] Example 2. 18 Synthesis of F-7Q-PSMA

[0055] Such as image 3 As shown, the reagents were separately installed in the following bottles before synthesis:

[0056] B1: 1 mL TBA-containing acetonitrile solution; B2: 2 mL acetonitrile; B3: 0.5 mg precursor dissolved in 0.5 mL DMF; B4: empty; B5: 7 mL HPLC mobile phase; B6: 10 mL 0.5 mol / L NaHCO 3 .

[0057] Put 800mCi of 18 F ions are transmitted from the accelerator to the QMA column, start the automatic program, and run automatically under the control of the computer: use the acetonitrile solution containing TBA in the B1 bottle to rinse the QMA column into the reaction tube, heat, ventilate and azeotrope to remove water with acetonitrile, and then Add the acetonitrile solution in the bottle B2 to remove water repeatedly, cool to 45°C, add the precursor in the bottle B3, perform a nucleophilic reaction at 50°C for 5 minutes, add the HPLC mobile phase in the bottle B5, and prepare the upper half of the mixture for HP...

Embodiment 318

[0060] Example 3. 18 Synthesis of F-FMSIO

[0061] Such as image 3 As shown, the reagents were separately installed in the following bottles before synthesis:

[0062] B1: 1mL acetonitrile solution containing K2.2.2; B2: 2mL acetonitrile; B3: 5mg precursor dissolved in 1mL acetonitrile; B4: 2ml 1mol / L hydrochloric acid; B5: 1mL 2mol / L NaOH and 5mL HPLC mobile phase mixture; B6: Empty .

[0063] The 1940mCi 18 F ions are transmitted from the accelerator to the QMA column, start the automatic program, and run automatically under the control of the computer: wash the QMA column with the acetonitrile solution containing K2. Then add the acetonitrile solution in bottle B2 to remove water repeatedly, cool down, add the precursor in bottle B3, nucleophilic reaction at 115°C for 5 minutes, then add hydrochloric acid solution in bottle B4, hydrolyze at 110°C for 5 minutes, add the fluid in bottle B5 After the phase mixed solution, the upper half of the mixed solution is prepared ...

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Abstract

The invention relates to a clinical single-tube fluorine-18 multifunctional modular equipment and radiopharmaceutical synthesis process, including a fluorine-18 ion capture and release module, a high performance liquid chromatography column purification module, a product collection module, and a high performance liquid chromatography column purification The module uses the liquid that can be injected intravenously as the HPLC mobile phase. The QMA column of the fluorine-18 ion capture and release module captures the fluorine-18 ions generated from the accelerator. The eluent and the drug precursor of the QMA column enter the reaction tube and the HPLC respectively. The mobile phase is mixed, the reaction tube is connected to the HPLC separation column of the high performance liquid chromatography column purification module, and the HPLC separation column is connected to the product collection module, and the product after online dilution and sterile filter membrane can be used for intravenous injection. By adopting the equipment and process of the present invention, the solvent conversion used in common modules can be avoided, the target compound can be collected correctly, and the pH value and radioactive concentration of the product can be adjusted on-line. Automated preparation.

Description

technical field [0001] The invention belongs to the synthesis technology of radiopharmaceuticals marked with fluorine-18, and specifically relates to a clinical single-tube fluorine-18 multifunctional modular equipment and a radiopharmaceutical synthesis process. Background technique [0002] 18 F-FDG is currently the most widely used clinical radiopharmaceutical, widely used in the diagnosis of various common diseases. but 18 F-FDG is glucose metabolism, which only reflects the glucose uptake and retention of organs and tumors. It has many deficiencies in actual clinical application, such as deficiencies in tumor receptors, tumor proliferation, and cell hypoxia imaging. There is an urgent clinical need for other positron radiopharmaceuticals to compensate for 18 Insufficiency of F-FDG. A variety of specific positron radiopharmaceuticals have been reported in the literature, such as those specific to prostate cancer: 18 F-DCFPyL, an imaging drug for Aβ deposition in the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/04
CPCB01D15/10B01J4/001B01J19/2415C07D213/73
Inventor 周彤
Owner 派特(北京)科技有限公司
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