Synthesis and characterization of the radiopharmaceutical [18F]fluoroestradiol
DOI:
https://doi.org/10.15392/bjrs.v9i1A.1387Keywords:
Radiopharmaceuticals, Breast Neoplasms, Product Synthesis, Quality ControlAbstract
[18F]Fluoroestradiol ([18F]FES), an estrogen analog, may be used in Positron Emission Tomography (PET) for evaluation of the tumor cell receptor profile in a noninvasive way, which is an important factor for determining the therapy to be used, disease staging, prognosis and response to therapy in breast cancer. [18F]FES is a new radiopharmaceutical and does not have an official monograph in any pharmacopeia until now. Therefore, the objective of this work was the optimization of the [18F]FES automatic synthesis and the elaboration of an analytical protocol for final product analyses. Initially, the synthesis of [18F]FES was performed according to a modified commercial protocol, using a TracerLab MXFDG synthesis module specific for [18F]FES synthesis. New protocols for the physicochemical quality control assays of the radiopharmaceutical were developed, including pH, chemical purity, residual solvents, radiochemical identity and purity. Physicochemical and microbiological analysis were performed with the synthesized [18F]FES at different time points to evaluate its stability. The uncorrected synthesis yield was 18.37 ± 3.07 %. All Quality Control methodologies proved to be effective for the product. The physicochemical and microbiological results obtained in the stability study showed that [18F]FES is stable during 8 hours after its synthesis, even under stress conditions. At the end of the study, it was concluded that the [18F]FES complies with all specifications required for a radiopharmaceutical intended for diagnostic use.Downloads
References
INCA – Instituto Nacional do Câncer José Alencar Gomes da Silva. Estimativa 2014: Incidência de Câncer no Brasil. Rio de Janeiro: INCA, 2014.
FLANAGAN, F. L.; DEHDASHTI, F.; SIEGEL, B. A. PET in Breast Cancer. Semin Nucl Med, v. 28, p. 290-302, 1998.
SURTI, S. Radionuclide Methods and Instrumentation for Breast Cancer Detection and Diagnosis. Semin Nucl Med, v. 43, p. 271-280, 2013.
CHANG, J. M.; LEE, H. J.; GOO, J. M.; LEE, H.; LEE, J. J.; CHUNG, J.; IM, J. False Positive and False Negative FDG-PET Scans in Various Thoracic Diseases. Korean J Radiol, v. 7, p. 57-69, 2006.
LINDEN, H. M. L.; DEHDASHTI, F. Novel Methods and Tracers for Breast Cancer Imaging. Semin Nucl Med, v. 43, p. 324-329, 2013.
SUNDARARAJAN, L.; LINDEN, H. M.; LINK, J. M.; KROHN, K. A.; MANKOFF, K. A. 18F-Fluoroestradiol. Semin Nucl Med, v. 37, p. 470-476, 2007.
KNOTT, K. E. ; GRÄTZ, D. ; HÜBNER, S. ; JÜTTLER, S. ; ZANKL, C. ; MÜLLER, M. Simplified and automatic one-pot synthesis of 16α-[18F]fluoroestradiol without high-performance liquid chromatography purification. J Labelled Compd Radiopharm, v. 54, p. 749-753, 2011.
ACKERMANN, U. ; TOCHON-DANGUY, H.; PONIGER, S. ; DAVIS, I. ; SCOTT, A. Synthesis of F-18 Fluoroestradiol using the FlexLab Radiosynthesizer. Melbourne : iPhase Technologies, 2015. Available at: <https://www.iphase.com.au/assets/fes-flexlab.pdf>. Last accessed: 16 Jun. 2020.
DIXIT, M. ; SHI, J. ; WEI, L. ; AFARI, G. ; BHATTACHARYYA, S. Synthesis of Clinical-Grade [18F]-Fluoroestradiol as a Surrogate PET Biomarker for the Evaluation of Estrogen Receptor-Targeting Therapeutic Drug. Int J Mol Imaging, v. 2013, article ID 278607, 2013.
KUMAR, P. ; MERCER, J. ; DOERKSON, C. ; TONKIN, K. ; MCEWAN, A. J. B. Clinical production, stability studies and PET imaging with 16-α-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patient. J Pharm Pharm Sci, v. 10, p. 256s-265s, 2007.
MORI, T. ; KASAMATSU, S. ; MOSDZIANOWSKI, C. ; WELCH, M. J. ; YONEKURA, Y. ; FUJIBAYASHI, Y. Automatic synthesis of 16α-[18F]fluoro-17β-estradiol using a cassette-type [18F]fluorodeoxyglucose synthesizer. Nucl Med Biol, v. 33, p. 281-286, 2006.
OH, S. J. ; CHI, D. Y. ; MOSDZIANOWSKI, C. ; KIL, H. S. ; RYU, J. S. ; MOON, D. H. The automatic production of 16α-[18F]fluoroestradiol using a conventional [18F]FDG module with a disposable cassette system. Appl Radiat Isot, v. 65, p. 676-681, 2007.
RÖMER, J. ; FÜCHTNER, F. ; STEINBACH, J. ; JOHANNSEN, B. Automated Production of 16α-[18F]Fluoroestradiol for Breast Cancer Imaging. Nucl Med Biol, v. 26, p. 473-479, 1999.
TEWSON, T. J. ; MANKOFF, D. A. ; PETERSON, L. M. ; WOO, I. ; PETRA, P. Interactions of 16α-[18F]-Fluoroestradiol (FES) with Sex Steroid Binding Protein (SBP). Mol Med Biol, v. 26, p. 905-913, 1999.
ZHOU, D. ; LIN, M. ; YASUI, N. ; AL-QAHTANI, M. H. ; DENCE, C. S. ; SCHWARZ, S. ; KATZENELLENBOGEN, J. A. Optimization of the preparation of fluorine-18-labeled steroid receptor ligands 16alpha-[18F]fluoroestradiol (FES), [18F]fluorofuranylnorprogesterone (FFNP), and 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) as radiopharmaceuticals. J Labelled Compd Radiopharm, v. 57, p. 371-377, 2014.
KUNTZSCH, M. ; LAMPARTER, D. ; BRÜGGENER, N. ; MÜLLER, M. ; KIENZLE, G. J. ; REISCHL, G. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals. Pharmaceuticals, v. 7, p. 621-633, 2014.
BISPO, A. C. A. ; NASCIMENTO, L. T. C. ; COSTA, F. M. ; SILVA, J. B. ; MAMEDE, M. Development of an HPLC method for the radiochemical purity evaluation of [18F]fluoroestradiol. Braz J Radiat Sci, v. 7, p. 01-09, 2019.
UNITED STATES PHAMACOPEIAL CONVENTION. USP/NF 2020 – United States Phamacopeia/National Formulary, 43rd ed, Rockville : United States Pharmacopeia, 2020.
Published
Issue
Section
License
Copyright (c) 2021 Brazilian Journal of Radiation Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
Licensing: The BJRS articles are licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
How to Cite
