A method of synthesizing an F-labeled compound, apparatus, and system 18 Method, apparatus and system for synthesis of F-labelled compounds

Abstract

This application relates to the field of radiolabeling, specifically to a type of... 18 A method, apparatus, and system for synthesizing F-labeled compounds. The method includes: a) mixing F-labeled compounds with... 18 H2 of F ions 18 a) The solution was transferred to the QMA solid-phase extraction column; b) The QMA solid-phase extraction column was eluted with 0.9% sodium chloride injection; c) The BBPA precursor was prepared, the chemical structure of which is shown in Formula I, and the BBPA precursor was labeled with the eluent; d) The labeled precursor was separated and purified by passing it through a C-18 semi-preparative chromatography column; e) Ethanol, hydrochloric acid, and 0.9% sodium chloride injection were added to the purified solution, mixed thoroughly, and filtered aseptically to obtain […]. 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II. This application also discloses... 18 An apparatus and system for synthesizing F-labeled compounds. The synthesis method of this invention has a simple purification process and can improve both radioactive and chemical purity.

Description

Technical Field

[0001] This disclosure relates to the field of radiolabeling, specifically to a type of... 18 Methods, apparatus and systems for synthesizing F-labeled compounds. Background Technology

[0002] Radiopharmaceuticals are compounds labeled with radioactive elements, suitable for in vivo administration to mammals, and used in medical imaging, diagnostic, or therapeutic applications. A radiopharmaceutical composition comprises a radiolabeled compound or a pharmaceutically acceptable salt thereof, a solvent, and one or more stabilizers.

[0003] Fluorine-18([ 18 [F] is a radioactive fluorine isotope of radiopharmaceuticals commonly used for diagnosis. Fluorine-18 decays via positron emission (97%) and electron capture (3%). With the radioactive isotope [ 18 The emitted positrons are attenuated by F and used for positron emission tomography (PET). This in vivo imaging method is particularly useful for cardiac imaging, tumor imaging, and brain imaging.

[0004] Currently, the most promising technique is the fluorine-fluorine exchange reaction in boron trifluoride. This technique involves dissolving the boron trifluoride precursor in solution, adding a 19F solution, and reacting for 20 minutes to achieve labeling. This method facilitates the exchange of free 18F with the 19F in the compound, thereby labeling the compound with 18F.

[0005] Automated synthesis systems are crucial for the production of radiopharmaceuticals. Existing synthesis modules, such as those from GE Healthcare, provide the production of radiopharmaceutical doses for clinical applications. The FASTlab synthesis module accepts and executes methods using equipment designed for the production of radiopharmaceuticals.

[0006] The existing technology involves dissolving BBPA in water, adding anhydrous ethanol and physiological saline, adjusting the pH with hydrochloric acid, quenching the reaction with physiological saline after completion, and then removing unreacted 18F through a Sep-Pak Alumina N Plus Light Cartridge to obtain the product.

[0007] However, the existing technologies have the following shortcomings: on the one hand, the existing methods have small reaction volumes and are not suitable for automated production; on the other hand, the existing methods use solid-phase extraction columns for purification, resulting in products with low chemical purity and a significant large impurity, which affects drug safety. Summary of the Invention

[0008] This invention provides 18 A method for synthesizing F-labeled compounds, the method comprising:

[0009] a, containing 18 H2 of F ions 18 The O solution was transported to the QMA solid-phase extraction column;

[0010] b. Elute the QMA solid-phase extraction column with 0.9% sodium chloride injection;

[0011] c. Prepare the BBPA precursor, whose chemical structure is shown in Formula I, and label the BBPA precursor with the elution buffer.

[0012]

[0013] d. The labeled precursor was separated and purified using a C-18 semi-preparative chromatography column;

[0014] e. Add ethanol, hydrochloric acid, and 0.9% sodium chloride injection to the purified solution, mix well, and filter aseptically to obtain [ 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II.

[0015]

[0016] In one embodiment of the present invention, the containing 18 H2 of F ions 18 The O solution is prepared by accelerator bombardment, wherein the bombardment process parameters are: proton pump energy of 18 MeV, bombardment beam current of 30–100 μA, and bombardment time of 5–120 min. In one embodiment of the present invention, when eluting the QMA solid-phase extraction column with 0.9% sodium chloride injection, the elution radioactivity is 1.4–2.2 Ci.

[0017] In one embodiment of the present invention, the specific steps for configuring the BBPA precursor are as follows:

[0018] Dissolve the BBPA compound in 0.9% sodium chloride injection, then add anhydrous ethanol and hydrochloric acid, and mix thoroughly.

[0019] In one embodiment of the present invention, the marking temperature is 85-98°C and the marking time is 10-20 min.

[0020] In one embodiment of the present invention, when the C-18 chromatographic column is used for separation and purification, the mobile phase is selected as 0.9% sodium chloride injection and anhydrous ethanol, with a mass ratio of 85:15 and a flow rate of 2-5 ml / min.

[0021] In one embodiment of the present invention, the radioactivity purity of the [18F]BF3-BPA injection product is greater than or equal to 95%, and the chemical purity is greater than or equal to 95%.

[0022] This invention provides another 18 An apparatus for synthesizing F-labeled compounds, the apparatus comprising:

[0023] 18 F-ion preparation unit, suitable for preparing F-ions containing 18 H2 of F ions 18 The O solution was transported to the QMA solid-phase extraction column;

[0024] 18 F ion enrichment unit, suitable for eluting QMA solid phase extraction column with 0.9% sodium chloride injection;

[0025] The labeling unit is suitable for preparing the BBPA precursor, whose chemical structure is shown in Formula I, and the BBPA precursor is labeled with the elution buffer.

[0026]

[0027] The HPLC purification unit is suitable for separating and purifying labeled precursors using a C-18 column;

[0028] The formulation preparation unit is suitable for adding ethanol, hydrochloric acid, and 0.9% sodium chloride injection to a purified solution, mixing thoroughly, and aseptically filtering to obtain […]. 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II.

[0029]

[0030] In one embodiment of the present invention, the device is an automated synthesis device, preferably a Trasis AllInOne automated synthesis device.

[0031] The present invention provides another method 18 A synthetic system for F-labeled compounds, said system comprising the […] as described in any one of claims 8-9 18 Device for product labeling of F]BF3-BPA injection solution.

[0032] The beneficial effects of this invention are:

[0033] 1. The technical method of this invention obtains an optimized purification process, improving radioactive purity and chemical purity.

[0034] 2. HPLC preparation replaces solid-phase extraction column purification, improving purity and adapting to automated production, achieving radioactive purity ≥95% and chemical purity ≥95%. The automated design improves production efficiency.

[0035] 3. Increase the volume of the reaction solvent, increase the amount of precursor feed, and increase the temperature to make the process more compatible with automated equipment.

[0036] 4. Compatible with Trasis AllInOne automated synthesis apparatus, fully automating 18F pretreatment, labeling reaction, purification and terminal preparation.

[0037] 5. By optimizing fluid control and online monitoring, batch-to-batch consistency is ensured to meet GMP production requirements. Attached Figure Description

[0038] To more clearly illustrate the technical solutions of the embodiments of this disclosure, the accompanying drawings of the embodiments will be briefly described below. Obviously, the drawings described below only relate to some embodiments of this disclosure and are not intended to limit the invention.

[0039] Figure 1 A kind of 18 Flowchart of the synthesis method for F-labeled compounds;

[0040] Figure 2 A kind of 18 Schematic diagram of the apparatus for synthesizing F-labeled compounds;

[0041] Figures 3a-3b A schematic diagram showing the radiochemical purity and chemical purity of the product in Example 1 is provided.

[0042] Figures 4a-4b A schematic diagram showing the radiochemical purity and chemical purity of the product in Example 2 is shown;

[0043] Figures 5a-5b A schematic diagram showing the radiochemical purity and chemical purity of the product in Example 3 is shown;

[0044] Figures 6a-6b A schematic diagram showing the radiochemical purity and chemical purity of the product in Example 4 is shown;

[0045] Figures 7a-7b A schematic diagram showing the radiochemical purity and chemical purity of the product in Example 5 is presented. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the described embodiments of this disclosure without creative effort are within the scope of protection of this invention.

[0047] This invention may be implemented in other specific forms without departing from its essential attributes. It should be understood that, without conflict, any and all embodiments of this invention can be combined with technical features of any or more other embodiments to obtain further embodiments. This invention includes such combinations to obtain further embodiments.

[0048] All publications and patents mentioned in this disclosure are incorporated herein by reference in their entirety. In the event of any conflict between the use or terminology used in any publications and patents incorporated by reference and the use or terminology used in this disclosure, the use and terminology of this disclosure shall prevail.

[0049] The chapter titles used in this article are for organizational purposes only and should not be construed as limiting the subject matter.

[0050] Unless otherwise specified, all technical and scientific terms used herein have their usual meaning in the field to which the claimed subject matter pertains. Where multiple definitions exist for a term, the definition herein shall prevail.

[0051] Unless otherwise stated, as used herein, the terms “comprising,” “containing,” or “including” mean that the element preceding the word encompasses the elements listed following the word and their equivalents, without excluding elements not described herein. The terms “containing” or “comprising (including)” as used herein can be open-ended, semi-closed, or closed-ended.

[0052] It should be further understood that compounds of formula (I) or pharmaceutically acceptable salts thereof can be isolated as solvates, and therefore any such solvates are included within the scope of this invention. For example, compounds of formula (I) or pharmaceutically acceptable salts thereof may exist in unsolvated forms as well as in solvated forms formed with pharmaceutically acceptable solvents (such as water, ethanol, etc.).

[0053] Example

[0054] The starting materials used in the examples are commercially available and / or can be prepared using various methods well known to those skilled in the art of organic synthesis. Those skilled in the art of organic synthesis will appropriately select the reaction conditions (including solvent, reaction atmosphere, reaction temperature, duration of the experiment, and post-treatment) from the synthetic methods described below. Those skilled in the art of organic synthesis will understand that the functional groups present on the various parts of the molecule should be compatible with the proposed reagents and reactions.

[0055] like Figure 1 As shown, a method is provided 18 A method for synthesizing F-labeled compounds, the method comprising:

[0056] will contain 18 H2 of F ions18 O solution was transferred to a QMA solid-phase extraction column; the QMA solid-phase extraction column was eluted; the prepared BBPA precursor was labeled with the eluent, and the labeled precursor was separated and purified by passing it through a C-18 semi-preparative chromatography column; finally, […]. 18 F]BF3-BPA injection product.

[0057] The BBPA precursor has the chemical structure shown in Formula I, and the product has the chemical structure shown in Formula II.

[0058]

[0059] like Figure 2 As shown, a method is provided 18 An apparatus for synthesizing F-labeled compounds, the apparatus comprising:

[0060] 18 F-ion preparation unit, suitable for preparing F-ions containing 18 H2 of F ions 18 The O solution was transported to the QMA solid-phase extraction column;

[0061] 18 F ion enrichment unit, suitable for eluting QMA solid phase extraction column with 0.9% sodium chloride injection;

[0062] The labeling unit is suitable for preparing the BBPA precursor, whose chemical structure is shown in Formula I, and the BBPA precursor is labeled with the elution buffer.

[0063]

[0064] The HPLC purification unit is suitable for separating and purifying labeled precursors using a C-18 column;

[0065] The formulation preparation unit is suitable for adding ethanol, hydrochloric acid, and 0.9% sodium chloride injection to a purified solution, mixing thoroughly, and aseptically filtering to obtain […]. 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II.

[0066]

[0067] The following detailed description is provided through specific embodiments.

[0068] Example 1

[0069] Dissolved in 18 O enrichment target water 1.554Ci[ 18 [F] fluoride ions pass through a QMA ion exchange column. [F] fluoride ions in the target water 18 [F] fluoride ions are adsorbed onto the ion exchange column. [F] fluoride ions are then adsorbed onto the column using 1.0 mL of 0.9% sodium chloride injection. 18F]fluoride ions are eluted from the QMA ion exchange column and added to the radioactivity reaction flask.

[0070] Add the BBPA solution (prepared with 0.9% sodium chloride injection, anhydrous ethanol, and hydrochloric acid solution) to a radioactivity reaction flask containing elution solution. Heat the resulting reaction mixture to 95°C and maintain the heating temperature at 95°C for 15 minutes. After the reaction is complete, cool the reaction mixture to 45°C.

[0071] The obtained [ 18 The F]BF3-BPA solution was transferred to a quantitative loop for semi-preparative purification. The chromatographic column was an XSelect HSS T3 OBD Prep Column, 5 μm, 10 × 250 mm. The mobile phase was a solution containing 85% 0.9% sodium chloride injection and 15% anhydrous ethanol. The flow rate was 2 mL / min.

[0072] The formulation step was performed using the Trasis AllInOne automated synthesis apparatus program, using approximately 21.5 mL of formulation solution to react with the collected purified [ 18 The HPLC mobile phase components of F]BF3-BPA were diluted to obtain [ 18 F]BF3-BPA injection.

[0073] The obtained [ 18 F]BF3-BPA injection solution, under nitrogen or helium pressure, passes through a 0.22μm... The sterile filter membrane was transferred to the final product vial. The time for complete sterile filtration was recorded as the synthesis end time. The radioactivity of the product vial was measured using an activity meter. The final product activity was 405.37 mCi.

[0074] like Figures 3a-3b As shown, the product, analyzed by HPLC, yielded a radiochemical purity of 97.15% (…). Figure 3a The chemical purity is 97.64%. Figure 3b ).

[0075] Example 2

[0076] Dissolved in 18 O enrichment target water 2.082Ci[ 18 [F] fluoride ions pass through a QMA ion exchange column. [F] fluoride ions in the target water 18 [F] fluoride ions are adsorbed onto the ion exchange column. [F] fluoride ions are then adsorbed onto the column using 1.0 mL of 0.9% sodium chloride injection. 18 F]fluoride ions are eluted from the QMA ion exchange column and added to the radioactivity reaction flask.

[0077] Add the BBPA solution (prepared with 0.9% sodium chloride injection, anhydrous ethanol, and hydrochloric acid solution) to a radioactivity reaction flask containing elution solution. Heat the resulting reaction mixture to 95°C and maintain the heating temperature at 95°C for 15 minutes. After the reaction is complete, cool the reaction mixture to 45°C.

[0078] The obtained [ 18 The F]BF3-BPA solution was transferred to a quantitative loop for semi-preparative purification. The chromatographic column was an XSelect HSS T3 OBD Prep Column, 5 μm, 10 × 250 mm. The mobile phase was a solution containing 85% 0.9% sodium chloride injection and 15% anhydrous ethanol. The flow rate was 2 mL / min.

[0079] The formulation step was performed using the Trasis AllInOne automated synthesis apparatus program, using approximately 21.5 mL of formulation solution to react with the collected purified [ 18 The HPLC mobile phase components of F]BF3-BPA were diluted to obtain [ 18 F]BF3-BPA injection.

[0080] The obtained [ 18 F]BF3-BPA injection solution, under nitrogen or helium pressure, passes through a 0.22μm... The sterile filter membrane was transferred to the final product vial. The time for complete sterile filtration was recorded as the synthesis end time. The radioactivity of the product vial was measured using an activity meter. The final product activity was 308.59 mCi.

[0081] like Figures 4a-4b As shown, the product, analyzed by HPLC, yielded a radiochemical purity of 97.53%. Figure 4a The chemical purity is 96.43%. Figure 4b ).

[0082] Example 3

[0083] Dissolved in 18 O enrichment target water 1.919Ci[ 18 [F] fluoride ions pass through a QMA ion exchange column. [F] fluoride ions in the target water 18 [F] fluoride ions are adsorbed onto the ion exchange column. [F] fluoride ions are then adsorbed onto the column using 1.0 mL of 0.9% sodium chloride injection. 18 F]fluoride ions are eluted from the QMA ion exchange column and added to the radioactivity reaction flask.

[0084] Add the BBPA solution (prepared with 0.9% sodium chloride injection, anhydrous ethanol, and 1% hydrochloric acid solution) to a radioactivity reaction flask containing elution solution. Heat the resulting reaction mixture to 95°C and maintain the heating temperature at 95°C for 15 minutes. After the reaction is complete, cool the reaction mixture to 45°C.

[0085] The obtained [18F]BF3-BPA solution was transferred to a quantitative loop for semi-preparative purification. The chromatographic column was an XSelectHSS T3 OBD Prep Column, 5 μm, 10 × 250 mm. The mobile phase was a solution containing 85% 0.9% sodium chloride injection and 15% anhydrous ethanol, and the flow rate was 2 mL / min.

[0086] The formulation step was performed using the Trasis AllInOne automated synthesis apparatus program. The collected HPLC mobile phase fraction containing purified [18F]BF3-BPA was diluted with approximately 21.5 mL of formulation solution to obtain […]. 18 F]BF3-BPA injection.

[0087] The obtained [18F]BF3-BPA injection solution was subjected to nitrogen or helium pressure through a 0.22 μm... The sterile filter membrane was transferred to the final product vial. The time for complete sterile filtration was recorded as the synthesis end time. The radioactivity of the product vial was measured using an activity meter. The final product activity was 354.42 mCi.

[0088] like Figures 5a-5b As shown, the product, analyzed by HPLC, yielded a radiochemical purity of 97.64% (…). Figure 5a The chemical purity is 97.66%. Figure 5b ).

[0089] Example 4

[0090] Dissolved in 18 O enrichment target water 2.145Ci[ 18 [F] fluoride ions pass through a QMA ion exchange column. [F] fluoride ions in the target water 18 [F] fluoride ions are adsorbed onto the ion exchange column. [F] fluoride ions are then adsorbed onto the column using 1.0 mL of 0.9% sodium chloride injection. 18 F]fluoride ions are eluted from the QMA ion exchange column and added to the radioactivity reaction flask.

[0091] Add the BBPA solution (0.9% sodium chloride injection, anhydrous ethanol, and hydrochloric acid solution) to a radioactivity reaction flask containing elution solution, then heat the resulting reaction mixture to 95°C and maintain the heating temperature at 95°C for 15 minutes. After the reaction is complete, cool the reaction mixture to 45°C.

[0092] The obtained [18F]BF3-BPA solution was transferred to a quantitative loop for semi-preparative purification. The chromatographic column was an XSelectHSS T3 OBD Prep Column, 5 μm, 10 × 250 mm. The mobile phase was a solution containing 85% 0.9% sodium chloride injection and 15% anhydrous ethanol, and the flow rate was 2 mL / min.

[0093] The formulation step was performed using the Trasis AllInOne automated synthesis apparatus program. The collected HPLC mobile phase fraction containing purified [18F]BF3-BPA was diluted with approximately 21.5 mL of formulation solution to obtain […]. 18 F]BF3-BPA injection.

[0094] The obtained [18F]BF3-BPA injection solution was subjected to nitrogen or helium pressure through a 0.22 μm... The sterile filter membrane was transferred to the final product vial. The time for complete sterile filtration was recorded as the synthesis end time. The radioactivity of the product vial was measured using an activity meter. The final product activity was 433.08 mCi.

[0095] like Figures 6a-6b As shown, the product, analyzed by HPLC, yielded a radiochemical purity of 97.39% (…). Figure 6a The chemical purity is 97.68%. Figure 6b ).

[0096] Example 5

[0097] Dissolved in 18 O enrichment target water 2.151Ci[ 18 [F] fluoride ions pass through a QMA ion exchange column. [F] fluoride ions in the target water 18 [F] fluoride ions are adsorbed onto the ion exchange column. [F] fluoride ions are then adsorbed onto the column using 1.0 mL of 0.9% sodium chloride injection. 18 F]fluoride ions are eluted from the QMA ion exchange column and added to the radioactivity reaction flask.

[0098] Add the BBPA solution (prepared with 0.9% sodium chloride injection, anhydrous ethanol, and hydrochloric acid solution) to a radioactivity reaction flask containing elution solution. Heat the resulting reaction mixture to 95°C and maintain the heating temperature at 95°C for 15 minutes. After the reaction is complete, cool the reaction mixture to 45°C.

[0099] The obtained [18F]BF3-BPA solution was transferred to a quantitative loop for semi-preparative purification. The chromatographic column was an XSelectHSS T3 OBD Prep Column, 5 μm, 10 × 250 mm. The mobile phase was a solution containing 85% 0.9% sodium chloride injection and 15% anhydrous ethanol, and the flow rate was 2 mL / min.

[0100] The formulation step was performed using the Trasis AllInOne automated synthesis apparatus program. The collected HPLC mobile phase fraction containing purified [18F]BF3-BPA was diluted with approximately 21.5 mL of formulation solution to obtain […]. 18 F]BF3-BPA injection.

[0101] The obtained [ 18 F]BF3-BPA injection solution, under nitrogen or helium pressure, passes through a 0.22μm... The sterile filter membrane was transferred to the final product vial. The time for complete sterile filtration was recorded as the synthesis end time. The radioactivity of the product vial was measured using an activity meter. The final product activity was 450.48 mCi.

[0102] like Figures 7a-7b As shown, the product, analyzed by HPLC, yielded a radiochemical purity of 97.06% (…). Figure 7a The chemical purity is 96.89%. Figure 7b ).

[0103] The above description is merely an exemplary embodiment of the present invention and is not intended to limit the scope of protection of the present invention, which is defined by the appended claims.

Claims

1. A kind 18 The method for synthesizing F-labeled compounds is characterized by, The method includes: a, containing 18 H2 of F ions 18 The O solution was transported to the QMA solid-phase extraction column; b. Elute the QMA solid-phase extraction column with 0.9% sodium chloride injection; c. Prepare the BBPA precursor, whose chemical structure is shown in Formula I, and label the BBPA precursor with the elution buffer. d. The labeled precursor was separated and purified using a C-18 semi-preparative chromatography column; e. Add ethanol, hydrochloric acid, and 0.9% sodium chloride injection to the purified solution, mix well, and filter aseptically to obtain [ 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II.

2. The synthesis method according to claim 1, characterized in that, The containing 18 H2 of F ions 18 O solution was prepared by accelerator bombardment, wherein the bombardment process parameters were: proton pump energy of 18 MeV, bombardment beam current of 30–100 μA, and bombardment time of 5–120 min.

3. The synthesis method according to claim 1, characterized in that, When eluting the QMA solid-phase extraction column with 0.9% sodium chloride injection, the elution radioactivity is 1.4–2.2 Ci.

4. The synthesis method according to claim 1, characterized in that, The specific steps for preparing the BBPA precursor are as follows: dissolve the BBPA compound in 0.9% sodium chloride injection solution, then add anhydrous ethanol and hydrochloric acid, and mix thoroughly.

5. The synthesis method according to claim 1, characterized in that, The marking temperature is 85–98℃, and the marking time is 10–20 min.

6. The synthesis method according to claim 1, characterized in that, When performing separation and purification using the C-18 chromatographic column, the mobile phase is 0.9% sodium chloride injection and anhydrous ethanol, with a mass ratio of 85:15, and the flow rate is 2-5 ml / min.

7. The synthesis method according to claim 1, characterized in that, The [ 18 The radioactive purity of F]BF3-BPA injection product is greater than or equal to 95%, and the chemical purity is greater than or equal to 95%.

8. A kind 18 An apparatus for synthesizing F-labeled compounds, characterized in that, The device includes: 18 F-ion preparation unit, suitable for preparing F-ions containing 18 H2 of F ions 18 The O solution was transported to the QMA solid-phase extraction column; 18 F ion enrichment unit, suitable for eluting QMA solid phase extraction column with 0.9% sodium chloride injection; The labeling unit is suitable for preparing the BBPA precursor, whose chemical structure is shown in Formula I, and the BBPA precursor is labeled with the elution buffer. The HPLC purification unit is suitable for separating and purifying labeled precursors using a C-18 column; The formulation preparation unit is suitable for adding ethanol, hydrochloric acid, and 0.9% sodium chloride injection to a purified solution, mixing thoroughly, and aseptically filtering to obtain […]. 18 The chemical structure of the F]BF3-BPA injection product is shown in Formula II.

9. The synthesis apparatus according to claim 8, characterized in that, The device is an automated synthesis device, preferably the Trasis AllInOne automated synthesis device.

10. A kind 18 A system for synthesizing F-labeled compounds, characterized in that, The system includes the [as described in any one of claims 8-9] 18 Device for product labeling of F]BF3-BPA injection solution.

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