GMP-compliant radiosynthesis of [\(^{18}\)F]GP1, a novel PET tracer for the detection of thrombi
- Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [\(^{18}\)F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific \(^{18}\)F-labeled small-molecule radiotracer that binds with high affinity to GPIIb/IIIa receptors of activated platelets. An improved, robust and fully automated radiosynthesis of [\(^{18}\)F]GP1 has been developed. [\(^{18}\)F]GP1 has been synthesized with decay corrected radiochemical yields of 38 \(\pm\) 6%, with a radiochemical concentration up to 1900 MBq/mL, molar activities of 952–9428 GBq/\(\mu\)mol and a radio-chemical purity >98%. After determination of the optimal reaction conditions, in particular for HPLC separation, adaption of the reaction conditions to PET center requirements, validation of the manufacturing process and the quality control methods, the synthesis of [\(^{18}\)F]GP1 was successfully implemented to GMP standards and was available for clinical application. We describe the GMP-compliant synthesis of the novel radiotracer [\(^{18}\)F]GP1. Moreover, we provide some proof-of-concept examples for clinical application in the cardiovascular field. PET/CT with the novel small-molecular radiotracer [18F]GP1 may serve as a novel highly sensitive tool for visualizing active platelet aggregation at the molecular level.
Author: | Verena HugenbergORCiDGND, Marion ZernaGND, Mathias BerndtGND, Reinhard ZabelGND, Rainer PreußGND, Dirk RolfsmeierGND, Janet WegenerGND, Henrik FoxORCiDGND, Astrid KassnerGND, Hendrik MiltingORCiDGND, Norman KoglinGND, Andrew W. StephensGND, Jan GummertORCiDGND, Wolfgang BurchertORCiDGND, Marcus-André DeutschGND |
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URN: | urn:nbn:de:hbz:294-88023 |
DOI: | https://doi.org/10.3390/ph14080739 |
Parent Title (English): | Pharmaceuticals |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/31 |
Date of first Publication: | 2021/07/28 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds BPVT; GMP compliant radiosynthesis; LVAD; PET/CT imaging; [18F]GP1; detection of thrombi; thrombosis |
Volume: | 14 |
Issue: | 8, Artikel 739 |
First Page: | 739-1 |
Last Page: | 739-17 |
Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Herz- und Diabeteszentrum NRW, Institut für Radiologie, Nuklearmedizin und molekulare Bildgebung |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |