Startseite Overcoming the obstacle of excess acetonitrile content in the final fluorine-18 radiotracers
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Overcoming the obstacle of excess acetonitrile content in the final fluorine-18 radiotracers

  • Mohammed Al-Qahtani ORCID logo EMAIL logo
Veröffentlicht/Copyright: 9. Januar 2024

Abstract

Acetonitrile is widely used as a solvent in synthesizing various fluorine-18 positron emission tomography (PET) radiotracers. Acetonitrile is classified as a Class II residual solvent, and due to its inherent toxic properties, the quantity of residual acetonitrile in drug products has to be limited. When working under Good Manufacturing Practices (GMP) during the radiosynthesis of a radiotracer, the aim is to control all solvent concentrations contained in the ready-to-use product. All products must meet predetermined specifications. Rarely, these limits may be exceeded. To avoid eliminating the entire batch, applying a straightforward time-based technique would be desirable to allow the majority of the product to be safely used. This technique should be based on determining a specific time and volume for which the radiotracer can be utilized in the patients after completing quality control analysis. Here, we report a very simple Excel sheet program based on existing mathematical equations that calculates the exact time and volume at which the radiotracer product can be safely administered to a patient.


Corresponding author: Mohammed Al-Qahtani, Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, E-mail:

Acknowledgments

The author thanks King Faisal Specialist Hospital and Research Centre (KFSH&RC) (RAC # 2130 022) and to Mohammad Shoaib Shawoo for his technical assistance.

  1. Research ethics: Not applicable.

  2. Author contributions: The author has accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The author state no conflict of interest.

  4. Research funding: None declared.

  5. Data availability: Not applicable.

References

1. Frey Frey, K. A., Royal, H. D., Di Carli, M. F., Dillehay, G. L., Gordon, L., Mankoff, D. A., O’Malley, J., Ramanna, L., Rohren, E., Segall, G. M., Shulkin, B. L., Wallis, J. W., Ziessman, H. A. ABNM position statement: nuclear medicine professional competency and scope of practice. J. Nucl. Med. 2011, 52, 994–997; https://doi.org/10.2967/jnumed.111.089979.Suche in Google Scholar PubMed

2. Mankoff, D. A. A definition of molecular imaging. J. Nucl. Med. 2007, 48, 18N–21N.Suche in Google Scholar

3. Vallabhajosula, S., Solnes, L., Vallabhajosula, B. A broad overview of positron emission tomography radiopharmaceuticals and clinical applications: what is new? Semin. Nucl. Med. 2011, 41, 246–264; https://doi.org/10.1053/j.semnuclmed.2011.02.003.Suche in Google Scholar PubMed

4. Rice, S. L., Roney, C. A., Daumar, P., Lewis, J. S. The next generation of positron emission tomography radiopharmaceuticals in oncology. Semin. Nucl. Med. 2011, 41, 265–282; https://doi.org/10.1053/j.semnuclmed.2011.02.002.Suche in Google Scholar PubMed PubMed Central

5. Schlyer, D. J. PET tracers and radiochemistry. Ann. Acad. Med. Singapore 2004, 33, 146–154; https://doi.org/10.47102/annals-acadmedsg.v33n2p146.Suche in Google Scholar

6. Gatley, S. J. Labeled glucose analogs in the genomic era. J. Nucl. Med. 2003, 44, 1082–1086.Suche in Google Scholar

7. Sharma, S., Krause, G., Ebadi, M. Radiation safety and quality control in the cyclotron laboratory. Radiat. Protect. Dosim. 2006, 118, 431–439; https://doi.org/10.1093/rpd/nci379.Suche in Google Scholar PubMed

8. Fowler, J. S., Ido, T. Initial and subsequent approach for the synthesis of 18FDG. Semin. Nucl. Med. 2002, 32, 6–12; https://doi.org/10.1053/snuc.2002.29270.Suche in Google Scholar PubMed

9. Nakao, R., Kida, T., Suzuki, K. Factors affecting quality control of [18F]FDG injection: bacterial endotoxins test, aluminum ions test and HPLC analysis for FDG and ClDG. Appl. Radiat. Isot. 2005, 62, 889–895; https://doi.org/10.1016/j.apradiso.2004.11.004.Suche in Google Scholar PubMed

10. Dantas, N. M., Nascimento, J. E., Santos-Magalhães, N. S., Oliveira, M. L. Radiolysis of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and the role of EtOH, radioactive concentration and temperature of storage. Appl. Radiat. Isot. 2013, 72, 158–162; https://doi.org/10.1016/j.apradiso.2012.10.017.Suche in Google Scholar PubMed

11. ICH Q3C(R%). Impurities: guidelines for residual solvents, 2016. www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Q3C__R6___Step_4.pdf.Suche in Google Scholar

12. United States Pharmacopeia. Fludeoxyglucose F-18 injection. In The United States Pharmacopeia, 30th ed., and The National Formulary, 25th ed.; United States Pharmacopeial Convention, Inc.: Rockville, MD, 2007; p. 2158.Suche in Google Scholar

13. Channing, M. A., Huang, B. X., Eckelman, W. C. Analysis of residual solvents in 2-[18F]FDG by GC. Nucl. Med. Biol. 2001, 28, 469–471; https://doi.org/10.1016/s0969-8051(00)00213-4.Suche in Google Scholar PubMed

14. Hung, J. Comparison of various requirements of the quality assurance procedures for [18F]FDG injection. J. Nucl. Med. 2002, 43, 1495–1506.Suche in Google Scholar

15. Kilian, K., Chabecki, B., Kiec, J., Kunka, A., Panas, B., Wójcik, M., Pekal, A. Synthesis, quality control and determination of metallic impurities in [18F]Fludeoxyglucose production process. Rep. Practical Oncol. Radiother. 2014, 19, 22–31; https://doi.org/10.1016/j.rpor.2014.03.001.Suche in Google Scholar PubMed PubMed Central

16. Kilian, K., Pekal, A., Szkutnik, W., Pyrzyńska, K. A fast method for the determination of residual solvents in [18F]FDG and 11C-methionine samples. Microchem. J. 2014, 115, 95–99; https://doi.org/10.1016/j.microc.2014.02.013.Suche in Google Scholar

17. Mihon, M., Tuta, C., Leonte, R., Ion, A. C., Lavric, V., Niculae, D. An Improved methodology for determination of radiochemical and chemical impurities in the synthesis process of [18F]FDG (2-[18F]fluoro-2–2deoxy-D-glucose). Environ. Eng. Manag. J. 2015, 14, 289–296; https://doi.org/10.30638/eemj.2015.028.Suche in Google Scholar

18. Rocheleau, M.-J., Titley, M., Bolduc, J. Measuring residual solvents in pharmaceutical samples using fast gas chromatography techniques. J. Chromatogr. B 2004, 805, 77–86; https://doi.org/10.1016/j.jchromb.2004.02.018.Suche in Google Scholar PubMed

19. Kapil, M., Lata, S. A review: residual solvents and various effective gas chromatographic techniques in the analysis of residual solvent. Int. J. Pharma Res. Rev. 2013, 2, 25–40.Suche in Google Scholar

20. Tankiewicz, M., Namiesnik, J., Sawicki, W. Analytical procedures for quality control of pharmaceuticals in terms of residual solvents CONTENT: challenges and recent developments. Trends Anal. Chem. 2016, 80, 328–344; https://doi.org/10.1016/j.trac.2015.09.008.Suche in Google Scholar

21. Koziorowski, J. A. Simple method for the quality control of [18F]FDG. Appl. Radiat. Isot. 2010, 68, 1740–1742; https://doi.org/10.1016/j.apradiso.2010.03.006.Suche in Google Scholar PubMed

22. Lins, C. L. R., Cassia, D. E. S. N. N., Alves, P. S., Eudes, D. N. J., Liane, D. O. M. Assessment of ethanol and acetonitrile in [18F]FDG preparations by means of liquid chromatography. J. Liq. Chromatogr. Relat. Technol. 2018, 41, 122–128; https://doi.org/10.1080/10826076.2018.1426598.Suche in Google Scholar

23. United States Pharmacopeia. Chapter 467, “Residual Solvents”; United States Pharmacopoeia (USP) 38, 2015; pp. 309–321.Suche in Google Scholar

24. United States, Pharmacopeia. Official Monograph, “Fludeoxyglucose F-18 Injection”; USP 38, 2015; pp. 3544–3546.Suche in Google Scholar

25. European Pharmacopoeia (EP). Chapter 5.4, “Residual Solvents”; European Pharmacopoeia (Ph. Eur.) 8.0, 2014; pp. 639–648.Suche in Google Scholar

26. European Pharmacopoeia (EP). Official Monograph, “Fludeoxyglucose F-18 Injection. Ph. Eur. 2014, 8, 1052–1054.Suche in Google Scholar

27. Hung Joseph, C. Comparison of various requirements of the quality assurance procedures for [18F]FDG injection. J. Nucl. Med. 2002, 43, 1495–1506.Suche in Google Scholar

28. Balaram, V. Recent advances in the determination of elemental impurities in pharmaceuticals – status, challenges and moving frontiers. Trends Anal. Chem. 2016, 80, 83–95; https://doi.org/10.1016/j.trac.2016.02.001.Suche in Google Scholar

29. APhA-APPM, Mahoney, D. W., McGough, C. G. Alternative Radiochemical Purity Testing Procedures for the Compounded Radiopharmaceuticals Approved from 1988; APhA: Washington, DC, 1998.Suche in Google Scholar

30. Mahoney, WD, McGough, GC, The American Pharmaceutical Association – Academy of Pharmacy Practice and Management (APhA-APPM). Alternative Radiochemical Purity Testing Procedures for the Compounded Radiopharmaceuticals Approved from 1988–1997; The American Pharmaceutical Association – Academy of Pharmacy Practice and Management (APhA-APPM): Washington, DC, 1998, 1998.Suche in Google Scholar

Received: 2023-08-28
Accepted: 2023-12-26
Published Online: 2024-01-09
Published in Print: 2024-02-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 29.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/ract-2023-0225/html
Button zum nach oben scrollen