Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7)
<b>Background:</b> The radiotracer [<sup>18</sup>F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an <sup>18</sup>F-labeled active ester as a prosthetic group, which...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/119 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587699236634624 |
|---|---|
| author | Philipp Krapf Thomas Wicher Boris D. Zlatopolskiy Johannes Ermert Bernd Neumaier |
| author_facet | Philipp Krapf Thomas Wicher Boris D. Zlatopolskiy Johannes Ermert Bernd Neumaier |
| author_sort | Philipp Krapf |
| collection | DOAJ |
| description | <b>Background:</b> The radiotracer [<sup>18</sup>F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an <sup>18</sup>F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18–25%, it is unsuitable for cassette-based systems with a single reactor. <b>Methods:</b> To simplify implementation on an automated synthesis module, the radiosynthesis of [<sup>18</sup>F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct (“late-stage”) radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with <i>ortho</i>-phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. <b>Results:</b> Overall, the new protocol enabled the production of [<sup>18</sup>F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [<sup>18</sup>F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. <b>Conclusions:</b> We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [<sup>18</sup>F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand. |
| format | Article |
| id | doaj-art-2e821586a5f8464fa3ab1c397bd3e555 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-2e821586a5f8464fa3ab1c397bd3e5552025-01-24T13:45:27ZengMDPI AGPharmaceuticals1424-82472025-01-0118111910.3390/ph18010119Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7)Philipp Krapf0Thomas Wicher1Boris D. Zlatopolskiy2Johannes Ermert3Bernd Neumaier4Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, GermanyForschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, GermanyForschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, GermanyForschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, GermanyForschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany<b>Background:</b> The radiotracer [<sup>18</sup>F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an <sup>18</sup>F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18–25%, it is unsuitable for cassette-based systems with a single reactor. <b>Methods:</b> To simplify implementation on an automated synthesis module, the radiosynthesis of [<sup>18</sup>F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct (“late-stage”) radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with <i>ortho</i>-phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. <b>Results:</b> Overall, the new protocol enabled the production of [<sup>18</sup>F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [<sup>18</sup>F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. <b>Conclusions:</b> We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [<sup>18</sup>F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand.https://www.mdpi.com/1424-8247/18/1/119[<sup>18</sup>F]JK-PSMA-7positron emission tomography (PET)prostate cancer imagingradiofluorinationTrasis AllInOne (AIO) moduleautomation |
| spellingShingle | Philipp Krapf Thomas Wicher Boris D. Zlatopolskiy Johannes Ermert Bernd Neumaier Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) Pharmaceuticals [<sup>18</sup>F]JK-PSMA-7 positron emission tomography (PET) prostate cancer imaging radiofluorination Trasis AllInOne (AIO) module automation |
| title | Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) |
| title_full | Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) |
| title_fullStr | Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) |
| title_full_unstemmed | Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) |
| title_short | Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([<sup>18</sup>F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-<span style="font-variant: small-caps">l</span>-glutamic Acid ([<sup>18</sup>F]JK-PSMA-7) |
| title_sort | fully automated production of i s i 1 carboxy 5 6 sup 18 sup f fluoro 2 methoxynicotinamido pentyl carbamoyl span style font variant small caps l span glutamic acid sup 18 sup f jk psma 7 |
| topic | [<sup>18</sup>F]JK-PSMA-7 positron emission tomography (PET) prostate cancer imaging radiofluorination Trasis AllInOne (AIO) module automation |
| url | https://www.mdpi.com/1424-8247/18/1/119 |
| work_keys_str_mv | AT philippkrapf fullyautomatedproductionofisi1carboxy56sup18supffluoro2methoxynicotinamidopentylcarbamoylspanstylefontvariantsmallcapslspanglutamicacidsup18supfjkpsma7 AT thomaswicher fullyautomatedproductionofisi1carboxy56sup18supffluoro2methoxynicotinamidopentylcarbamoylspanstylefontvariantsmallcapslspanglutamicacidsup18supfjkpsma7 AT borisdzlatopolskiy fullyautomatedproductionofisi1carboxy56sup18supffluoro2methoxynicotinamidopentylcarbamoylspanstylefontvariantsmallcapslspanglutamicacidsup18supfjkpsma7 AT johannesermert fullyautomatedproductionofisi1carboxy56sup18supffluoro2methoxynicotinamidopentylcarbamoylspanstylefontvariantsmallcapslspanglutamicacidsup18supfjkpsma7 AT berndneumaier fullyautomatedproductionofisi1carboxy56sup18supffluoro2methoxynicotinamidopentylcarbamoylspanstylefontvariantsmallcapslspanglutamicacidsup18supfjkpsma7 |