RESEARCH ON THE INFLUENCE OF DIFFERENT TYPES OF ANION-EXCHANGE CARTRIDGES ON THE QUALITY OF [18F]NAF RADIOPHARMACEUTICAL AS PART OF PRODUCTION PROCESS DEVELOPMENT

Authors

  • Marija Atanasova Lazareva University Institute for positron-emission Tomography, Skopje, Republic of North Macedonia
  • Ana Ugrinska University Institute for positron-emission Tomography, Skopje, Republic of North Macedonia
  • Emilija Janevik-Ivanovska Faculty of Medical Sciences, Goce Delcev University- Stip, Republic of North Macedonia

DOI:

https://doi.org/10.35120/kij5404661a

Keywords:

[18F]Sodium fluoride, anion-exchange cartridges, pH, quality

Abstract

[18F]Sodium Fluoride radiopharmaceutical is a sterile solution for intravenous administration, intended
for skeletal visualization by positron emission tomography (PET). [18F]Sodium Fluoride for bone imaging was
introduced in early 1960's, but with the increased availability of PET scanners in the last two decades, this
radiopharmaceutical has growing use in clinical practice for the detection of bone metastases. The production
process of [18F]NaF includes production of the radioisotope [18F]F- and purification and formulation of the [18F]NaF
radiopharmaceutical. The radioisotope [18F]F- is produced by a cyclotron via the 18O(p,n)18F nuclear reaction,
followed by recovery of [18F]F- from [18O] proton-irradiated water by adsorption and desorption from anionexchange
resins. The fluoride anions are trapped on the anion-exchange SPE (solid-phase extraction) cartridge, and
all other cationic and water-soluble radionuclide impurities present in irradiated enriched water are collected in the
waste vial. Next step is desorption of the fluoride anions from the cartridge by elution with saline solution (0.9%
NaCl). This study aimed to define the most appropriate type of anion-exchange SPE cartridge which could be used
for routine production [18F]Sodium fluoride radiopharmaceutical which meets the quality requirements defined in
European pharmacopeia monograph. For that purpose, as part of development of in-house production method,
manual productions with four different types of anion-exchange cartridges were performed. The influence of sorbent
substrate and counter-ion of the cartridge on the final yield and the quality of the produced radiopharmaceutical was
investigated. The study also aimed to define the minimum volume of physiological solution required for the pH
parameter to be within limits.
The results have shown that the quality parameters: appearance, chemical purity, radiochemical purity and
radionuclide purity were in defined acceptance criteria and did not differ when using different anion-exchange
cartridges. The pH analyses have demonstrated that the type of cartridge and counter-ion influence the final pH of
[18F]NaF solution. This study confirmed that the three types of anion-exchange resins (QMA-Cl-, QMA-CO3
2- and
PS-OH-) could be used for production. In the experiments where QMA-Cl- was used, the required pH level was
obtained even without dilution. The other cartridges could be used in the [18F]NaF production process, but further
dilution is necessary in order to obtain the pH value in acceptance criteria. On the basis of this study, the QMA-Cl- is
chosen as a cartridge to be used in the further development of the in-house method for [18F]NaF radiopharmaceutical
production.

Author Biographies

Marija Atanasova Lazareva, University Institute for positron-emission Tomography, Skopje, Republic of North Macedonia

Faculty of Medical Sciences, Goce Delcev University- Stip

Ana Ugrinska, University Institute for positron-emission Tomography, Skopje, Republic of North Macedonia

Medical Faculty, University “Ss Cyril and Methodius Skopje, Republic of North Macedonia

References

Ahuja, K., Sotoudeh, H., Galgano, S. J., Singh, R., Gupta, N., Gaddamanugu, S., & Choudhary, G. (2020). 18F-Sodium Fluoride PET: History, Technical Feasibility, Mechanism of Action, Normal Biodistribution, and Diagnostic Performance in Bone Metastasis Detection Compared with Other Imaging Modalities. Journal of nuclear medicine technology, 48(1), 9–16.

Avila-Rodriguez, M. A., Jalilian, A. R., Korde, A., Schlyer, D., Haji-Saeid, M., Paez, J., & Perez-Pijuan, S. (2022). Current status on cyclotron facilities and related infrastructure supporting PET applications in Latin America and the Caribbean. EJNMMI radiopharmacy and chemistry, 7(1), 14.

Bastawrous, S., Bhargava, P., Behnia, F., Djang, D. S., & Haseley, D. R. (2014). Newer PET application with an old tracer: role of 18F-NaF skeletal PET/CT in oncologic practice. Radiographics : a review publication of the Radiological Society of North America, Inc, 34(5), 1295–1316.

Choi, J.Y., Lee, J.W., Lee, K., Kim, K., Seo, Y.B., Kim, J.Y., & Ryu, Y.H. (2016). Time and cost effective production of sodium [18F]fluoride using a dedicated automation module with disposable cassettes for GMP environment. Journal of Radioanalytical and Nuclear Chemistry, 309, 983-987.

Collet, C., Otabashi, M., Giacomelli, F., Veran, N., Karcher, G., Chapleur, Y., & Lamandé-Langle, S. (2015). Fully automated production of sodium [(18)F]fluoride on AllInOne and miniAllInOne synthesizers. Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine, 102, 87–92

Cook, G., & Goh, V. (2020). Molecular Imaging of Bone Metastases and Their Response to Therapy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine, 61(6), 799–806.

European Pharmacopoeia 10.0, (2020) monograph no. 2100 „Sodium Fluoride (18F) injection“(01/2008:2100)

EUROPEAN UNION, EudraLex: The Rules Governing Medicinal Products in the European Union. (2008). Volume 4, EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Annex 3: Manufacture of Radiopharmaceuticals.

Gillings, N., Hjelstuen, O., Ballinger, J., Behe, M., Decristoforo, C., Elsinga, P., Ferrari, V., Peitl, P. K., Koziorowski, J., Laverman, P., Mindt, T. L., Neels, O., Ocak, M., Patt, M., & Todde, S. (2021). Guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. EJNMMI radiopharmacy and chemistry, 6(1), 8.

Hockley, B. G., & Scott, P. J. (2010). An automated method for preparation of [(18)F]sodium fluoride for injection, USP to address the technetium-99m isotope shortage. Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine, 68(1), 117–119.

INTERNATIONAL ATOMIC ENERGY AGENCY. (2012). Cyclotron Produced Radionuclides: Guidance on Facility Design and Production of [18F]Fluorodeoxyglucose (FDG). IAEA, Vienna

Jacobson, M.S., Steichen, R.A., Peller, P.J. (2012). PET Radiochemistry and Radiopharmacy. In: Peller, P., Subramaniam, R., Guermazi, A. (eds) PET-CT and PET-MRI in Oncology. Medical Radiology(). Springer, Berlin, Heidelberg.

Jadvar, H., Desai, B., & Conti, P. S. (2015). Sodium 18F-fluoride PET/CT of bone, joint, and other disorders. Seminars in nuclear medicine, 45(1), 58–65.

Kao, C. H., Hsu, W. L., Kao, P. F., Lan, W. C., Xie, H. L., Lin, M. C., & Chao, H. Y. (2010). An efficient and aseptic preparation of "sodium fluoride ((18)F) injection" in a GMP compliant facility. Annals of nuclear medicine, 24(3), 149–155.

Kilbourn, M.R., Rodnick, M.E. and Clark, M. (2020). Production of Short Half-Life PET Radionuclides. In Handbook of Radiopharmaceuticals (eds P. Scott and M. Kilbourn).

Langsteger, W., Rezaee, A., Pirich, C., & Beheshti, M. (2016). 18F-NaF-PET/CT and 99mTc-MDP Bone Scintigraphy in the Detection of Bone Metastases in Prostate Cancer. Seminars in nuclear medicine, 46(6), 491–501.

Miele, E., Spinelli, G. P., Tomao, F., Zullo, A., De Marinis, F., Pasciuti, G., Rossi, L., Zoratto, F., & Tomao, S. (2008). Positron Emission Tomography (PET) radiotracers in oncology--utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC). Journal of experimental & clinical cancer research : CR, 27(1), 52.

Mihon, M., Tuța, C., Lavric, V., Niculae, D., & Drăgănescu, D. (2015). Quality control and stability study of the sodium fluoride injection [18f]NaF, September Farmacia 63(5):765-769

Visioni, A., & Kim, J. (2011). Positron emission tomography for benign and malignant disease. The Surgical clinics of North America, 91(1), 249–266.

Wang, Y., Chen, D., Augusto, R., Liang, J., Qin, Z., Liu, J., & Liu, Z. (2022). Production Review of Accelerator-Based Medical Isotopes. Molecules (Basel, Switzerland), 27(16), 5294.

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Published

2022-09-30

How to Cite

Atanasova Lazareva, M., Ugrinska, A., & Janevik-Ivanovska, E. (2022). RESEARCH ON THE INFLUENCE OF DIFFERENT TYPES OF ANION-EXCHANGE CARTRIDGES ON THE QUALITY OF [18F]NAF RADIOPHARMACEUTICAL AS PART OF PRODUCTION PROCESS DEVELOPMENT. KNOWLEDGE - International Journal, 54(4), 661–667. https://doi.org/10.35120/kij5404661a

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