NÜKLEER TIP PET KİMYASINDAKİ 68GAPSMA-11 RADYOFARMASÖTİK BİLEŞİMİNDEKİ METALİK KİRLİLİKLER ÜZERİNDE 68Ge/68Ga JENERATÖRÜNÜN ÖN ELÜSYON ETKİNLİĞİNİN DEĞERLENDİRİLMESİ

Year 2021, , 526 - 530, 01.10.2021

Ayşe Uğur , Doğangün Yüksel

https://doi.org/10.26650/IUITFD.2021.872398

Abstract

Amaç: Metalik safsızlıkların varlığı, özellikle radyoaktif etiketlemede mümkün olan en yüksek spesifik aktiviteyi gerektiren reseptöre özgü biyomoleküllerle etkileşimleri nedeniyle ciddi bir endişe oluşturabilir. Jeneratörün uzun süre kullanılmaması durumunda Zn ve diğer toksik metal kirliliğinin arttığı çalışmalar da bulunmaktadır. Bu çalışmada ön elüsyonun sentez ürünündeki kimyasal ve radyokimyasal safsızlıklar üzerindeki etkisi araştırılmıştır. Gereç ve Yöntemler: Çalışmada, 68GaPSMA-11 işaretlemesi, bir ay kullanılmayan jeneratör eluatı (örnek 1) ile yapıldı. Jeneratör kullanıldıktan 24 saat sonra boş bir elüsyon alındı (örnek 2). 24 saat içinde, ikinci 68GaPSMA-11 işaretlemesi gerçekleştirildi (örnek 3). Bu etiketlemeden 6 saat sonra başka bir 68GaPSMA- 11 sentezi gerçekleştirildi (numune 4). Elüatlar, Endüktif Olarak Birleştirilmiş Plazma Kütle Spektrometresi (ICP-MS) ile analiz edildi. Bulgular: Sonuçlar μg/ml cinsinden tablo olarak rapor edildi. İşaretli ürünlerde 0.018 ppm, 0.012 ppm ve 0.009 ppm seviyelerinde belirlenen 68Ge seviyeleri farmakope limitlerinin altında belirlendi. Jeneratör ön elüsyonu yapılmadan yapılan işaretlemede Zn(II) kirliliği 0.625 ppm bulundu. Önceden yıkanmış jeneratör eluatı ile işaretlemelerde; Zn(II) kirliliği 0.133 ppm ve 0.108 ppm olarak belirlenmiştir. Sonuç: Jeneratörün sentezden önce ön elüsyonu, çinko kirliliği dışında kimyasal bir gereklilik gibi görünmemektedir. 68GaPSMA- 11, yüksek işaretleme etkinliği için önceden ayrıştırılabilir, ancak ön elüsyonun kimyasal ve radyokimyasal kontaminasyon açısından önemli olmadığı düşünülmektedir.

Keywords

Radyofarmasötik ürün, 68GaPSMA-11, metalik safsızlık, 68Ge/68Ga jeneratör

EVALUATION OF 68Ge/68Ga GENERATOR PRE-ELUTION EFFICIENCY ON METALLIC IMPURITIES IN THE COMPOSITION OF 68GaPSMA-11 RADIOPHARMACEUTICAL IN NUCLEAR MEDICINE PET CHEMISTRY

Abstract

Objective: The presence of metallic impurities can pose a serious concern due to their interaction with receptor-specific biomolecules that require the highest possible specific activity, especially in radioactive labeling. There are studies in which Zn and other toxic metal pollution increases if the generator is not used for a long time. In this study the effect of pre-elution on chemical and radiochemical impurities in the synthesis product was investigated. Material and Methods: In the study, 68GaPSMA-11 labeling was performed with the generator eluate that was not used for one month (sample 1). A blank elution was taken 24 hours after using the generator (sample 2). In the next 24 hours, the second 68GaPSMA- 11 labeling was performed (sample 3). Six hours after this labeling, another 68GaPSMA-11 synthesis was performed (sample 4). Eluates were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: Results was reported as a table in μg/ml. 68Ge levels determined at 0.018 ppm, 0.012 ppm and 0.009 ppm levels in the labeled products were determined below the pharmacopoeia limits. Zn(II) impurities were found as 0.625 ppm in the labeling performed without generator pre-elution. In generator pre-eluted labelings; Zn(II) impurities were determined as 0.133 ppm and 0.108 ppm. Conclusion: Pre-elution of the generator prior to synthesis does not seem to be a chemical requirement other than zinc pollution. 68GaPSMA-11 can be pre-eluted for high labeling efficiency, but it is thought that pre-elution is not significant in terms of chemical and radiochemical contamination.

Keywords

Radiopharmaceutical product, 68GaPSMA-11, metallic impurities, 68Ge/68Ga generator

References

• 1. Greene MW, Tucker W. An improved gallium-68 cow. Appl Radiat Isot 1961;12(1-2): 62-3. [CrossRef]
• 2. Roesch F. Maturation of a Key Resource–The Germanium-68/ Gallium-68 Generator: Development and New Insights. Curr Radiopharm 2012;5(3):202-11. [CrossRef]
• 3. Velikyan I, Antoni G, Sörensen J, Estrada S. Organ biodistribution of Germenium-68 in rest in the oresence and absence of [(68)Ga] Ga-DOTA-TOC for the extrapolation to the human organ and wholebody radration dosimetry. Am J Nucl Med Mol Imaging 2013;3(2):154-65.
• 4. Velikyan, I. 68Ga-Based radiopharmaceuticals: production and application relationship. Molecules 2015;20(7):12913- 43. [CrossRef]
• 5. Uğur, A. Yaylalı, O. Yüksel, D. Examination of metallic impurities of 68Ge/68Ga generators used for radioactive labeling of peptides in clinical PET applications. Nucl Med Commun 2021;42(1):81-5. [CrossRef]
• 6. Vyas CK, Lee JY, Hur MG, Yang SD, Kong YB, Lee EJ, et al. Chitosan-TiO2 composite: A potential 68Ge/68Ga generator column material. Appl Radiat Isot 2019;149:206- 13. [CrossRef]
• 7. Rosech F. Past, present and future of 68Ge/68Ga generators, Appl Radiat Isot. 2013;76:24-30. [CrossRef]
• 8. Chakraborty U, George CM, Lyndaker AM, Alani E. A. Delicate balance between repair and replication factors regulates recombination between divergent dna sequences in saccharomyces cerevisiae. Genetics 2016;202(2):525-40. [CrossRef]
• 9. Asti M, De Pietri G, Fraternali A, Grassi E, Sghedoni R, Fioroni F, et al. Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC, Nucl Med Biol 2008;35(6):721-24. [CrossRef]
• 10. Mueller WM, Blackledge JP, Libowitz GG. Metal Hydrides, Academic Press, New York 1968, p. 542-46
• 11. Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007;48(10):1741–8. [CrossRef]
• 12. Breeman WA, de Jong M, de Blois E, Bernard BF. Konijnenberg M, Krenning EP Radiolabelling DOTApeptides with 68Ga. Eur J Nucl Med Mol Imaging 2005;32(4):478-85. [CrossRef]
• 13. Chatalic KLS, Heskamp S, Konijnenberg M, Molkenboer- Kuenen JDM, Franssen GM, Clahsen-van Groningen MC, et al. Towards personalized treatment of prostate cancer: PSMA I&T, a promising prostate-specific membrane, antigen-targeted theranostic agent, Theranostics, 2016;6(6): 849-61. [CrossRef]
• 14. Rahbar K, Afshar-Oromieh A, Jadvar H, Ahmadzadehfar H. PSMA Theranostics: Current status and future directions, Mol Imaging 2018;17:1536012118776068. [CrossRef]
• 15. Prasad V, Steffen IG, Diederichs G, Makowski MR, Wust P, Brenner W. Biodistribution of [(68)Ga]PSMA-HBED-CC in patients with prostate cancer: Characterization of uptake in normal organs and tumour lesions. Mol Imaging Biol 2016;18(3):428-36. [CrossRef]
• 16. Elri T, Aras M, Salihoglu YS, Erdemir RU, Çabuk M. A potential pitfall in the use of 68Ga-PSMA PET/CT: Anthracosis. Rev Esp Med Nucl Imagen Mol 2017;36(1):65- 6. [CrossRef]
• 17. Vamadevan S, Shetty D, Le K, Chuong B, Mansberg R, Loh H. Prostate-Specific Membrane Antigen(PSMA) Avid Pancreatic Neuroendocrine Tumor Clin Nucl Med 2016;41(10):804-6. [CrossRef]
• 18. European Pharmacopoeia Commission, Council of Europe. European 7 pharmacopoeia. 8th ed. Strasbourg: European Directorate for the Quality of Medicines & Health Care 2013.
• 19. Abernethy DR , Destefano AJ , Cecil TL, Zaidi K , Williams RL. Metal impurities in food and drugs. Pharm Res 2010;27(5):750-5. [CrossRef]