CELL INCORPORATION STUDY OF [99mTc]Tc-NAB-PACLITAXEL ON HUMAN COLORECTAL ADENOCARCINOMA CELL LINE

Year 2023, Volume: 47 Issue: 1, 133 - 140, 20.01.2023

Meliha Ekinci , Derya İlem-özdemir

https://doi.org/10.33483/jfpau.1166949

Abstract

Objective: The development of new radiopharmaceuticals capable of specifically imaging cancer is an important research area. For this reason, the aim of this study is to investigate cell binding of novel developed nanoradiopharmaceutical ([99mTc]Tc-nab-PTX) on HT-29 cell line (human colorectal adenocarcinoma cells).
Material and Method: In this study, nab-PTX was labeled with [99mTc]Tc, and labeling efficiency and in vitro stability were investigated by radioactive thin layer chromatography (RTLC). Then, cell incorporation of [99mTc]Tc-nab-PTX was performed using HT-29 cell line.
Result and Discussion: According to obtained results, nab-PTX was labeled with high radiochemical purity (>99%). The [99mTc]Tc-nab-PTX was found to be stable in saline for 6-h, and in cell medium up to 2-h. It was determined that [99mTc]Tc-nab-PTX had a greater cell binding activity on HT-29 cells than R/H-[99mTc]NaTcO4 at 30 min. The results were found to be promising for future in vivo studies with [99mTc]Tc-nab-PTX.

Keywords

HT29 cell line, nab-paclitaxel, radiolabeling, technetium-99m

Supporting Institution

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Project Number

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Thanks

The authors thank to Ege University Nuclear Medicine Department for obtaining [99mTc]Tc and to Prof. Dr. Emel Öykü Çetin Uyanıkgil for providing cell line.

[99mTc]Tc-NAB-PAKLİTAKSEL'İN İNSAN KOLOREKTAL ADENOKARSİNOMA HÜCRE HATTI ÜZERİNDE HÜCRE BAĞLANMA ÇALIŞMASI

Abstract

Amaç: Spesifik olarak kanseri görüntüleyebilen yeni radyofarmasötiklerin geliştirilmesi önemli bir araştırma alanıdır. Bu nedenle bu çalışmanın amacı, yeni geliştirilen nanoradyofarmasötiğin ([99mTc]Tc-nab-PTX) HT-29 hücre hattına (insan kolorektal adenokarsinom hücreleri) hücre bağlanmasını araştırmaktır.
Materyal ve Metot: Bu çalışmada, nab-PTX [99mTc]Tc ile işaretlenmiş ve işaretleme etkinliği ve in vitro stabilitesi radyoaktif ince tabaka kromatografisi (RTLC) ile araştırılmıştır. Daha sonra, [99mTc]Tc-nab-PTX'in hücre bağlanması, HT-29 hücre hattı kullanılarak gerçekleştirilmiştir.
Sonuç ve Tartışma: Elde edilen sonuçlara göre, nab-PTX yüksek radyokimyasal saflıkla (>%99) radyoişaretlenmiştir. [99mTc]Tc-nab-PTX'in oda sıcaklığında 6 saate kadar ve hücre ortamında 2 saate kadar stabil olduğu bulunmuştur. [99mTc]Tc-nab-PTX'in HT-29 hücreleri üzerinde 30. dakikada R/H-[99mTc]NaTcO4'ten daha yüksek bir hücre bağlama aktivitesine sahip olduğu belirlenmiştir. Sonuçların [99mTc]Tc-nab-PTX ile gelecek in vivo çalışmalar için umut verici olduğu bulunmuştur.

Keywords

HT29 hücre hattı, nab-paklitaksel, radyoişaretleme, teknesyum-99m

Project Number

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References

• 1. Siegel, R. L., Miller, K. D., Fuchs, H. E., Jemal, A. (2022). Cancer statistics, 2022. CA: A Cancer Journal for Clinicians, 72(1), 7–33. [CrossRef]
• 2. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. [CrossRef]
• 3. Smith, N., Webb, A. (2010). Nuclear Medicine: Planar Scintigraphy, SPECT and PET/CT. In: N. Smith and A. Webb (Eds.), Introduction to Medical Imaging: Physics, Engineering and Clinical Applications, (pp. 89-144). Cambridge: Cambridge University Press. [CrossRef]
• 4. Kim, E. E. (2013). Radiopharmaceuticals in nuclear pharmacy and nuclear medicine. Journal of Nuclear Medicine, 54(2), 324-325. [CrossRef]
• 5. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü. (2019). Türkiye Kanser İstatistikleri 2016. From https://hsgm.saglik.gov.tr/depo/birimler/kanser-db/istatistik/Trkiye_Kanser_statistikleri_2016.pdf Erişim tarihi: 01.08.2022.
• 6. Montminy, E. M., Jang, A., Conner, M., Karlitz, J. J. (2020). Screening for colorectal cancer. Medical Clinics of North America, 104(6), 1023–1036. [CrossRef]
• 7. Stockenhuber, K., East, J. E. (2019). Colorectal cancer: prevention and early diagnosis. Medicine (United Kingdom), 47(7), 395–399. [CrossRef]
• 8. Brigger, I., Dubernet, C., Couvreur, P. (2002). Nanoparticles in cancer therapy and diagnosis. Advanced Drug Delivery Reviews, 54(5), 631–651. [CrossRef]
• 9. Gradishar, W. J., Krasnojon, D., Cheporov, S., Makhson, A. N., Manikhas, G. M., Clawson, A., Bhar, P., McGuire, J. R., Iglesias, J. (2012). Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: Final analysis of overall survival. Clinical Breast Cancer, 12(5), 313–321. [CrossRef]
• 10. Gradishar, W. J., Krasnojon, D., Cheporov, S., Makhson, A. N., Manikhas, G. M., Clawson, A., Bhar, P. (2009). Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. Journal of Clinical Oncology, 27(22), 3611–3619. [CrossRef]
• 11. Desai, N., Trieu, V., Yao, Z., Louie, L., Ci, S., Yang, A., Tao, C., De, T., Beals, B., Dykes, D., Noker, P., Yao, R., Labao, E., Hawkins, M., Soon-Shiong, P. (2006). Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clinical Cancer Research, 12(4), 1317–1324. [CrossRef]
• 12. Stinchcombe, T. E. (2007). Nanoparticle albumin-bound paclitaxel: A novel Cremphor-EL®-free formulation of paclitaxel. Nanomedicine, 2(4), 415–423. [CrossRef]
• 13. NCT03693677. (2018). First Line Metastatic Pancreatic Cancer : 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI.
• 14. Von Hoff, D. D., Ramanathan, R. K., Borad, M. J., Laheru, D. A., Smith, L. S., Wood, T. E., Korn, R. L., Desai, N., Trieu, V., Iglesias, J. L., Zhang, H., Soon-Shiong, P., Shi, T., Rajeshkumar, N. V., Maitra, A., Hidalgo, M. (2011). Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: A phase I/II trial. Journal of Clinical Oncology, 29(34), 4548–4554. [CrossRef]
• 15. Ekinci, M., İlem-Özdemir, D. (2021). Radyofarmasötikler ve teranostikler. J Lit Pharm Sci, 10(1), 119–132. [CrossRef]
• 16. Zolle, U. (2007). Technetium-99m Pharmaceuticals: Preparation and Quality Control in Nuclear Medicine. Springer Berlin, Heidelberg, p. 345. [CrossRef]
• 17. Çintaş, D. (2022). Master Thesis. Evaluation of the potential use of radiolabeled nab-paclitaxel in the diagnosis of breast cancer. Department of Radiopharmacy, Institute of Health Sciences, Ege University, Izmir, Turkiye.
• 18. Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., Bray, F. (2021). Cancer statistics for the year 2020: An overview. International Journal of Cancer, 10.1002/ijc.33588. [CrossRef]
• 19. Croce, C. M. (2008). Oncogenes and cancer. New England Journal of Medicine, 358, 502–511. [CrossRef]
• 20. Elgazzar, A. H. (2015). The Pathophysiologic Basis of Nuclear Medicine. Springer International Publishing, Switzerland, p.753. [CrossRef]
• 21. Diniz, S. O. F., Siqueira, C. F., Nelson, D. L., Martin-Comin, J., Cardoso, V. N. (2005). Technetium-99m ceftizoxime kit preparation. Brazilian Archives of Biology and Technology, 48(spe2), 89–96. [CrossRef]
• 22. Banerjee, I., Behera, A., De, K., Chattopadhyay, S., Sachdev, S. S., Sarkar, B., Ganguly, S., Misra, M. (2015). Synthesis, characterization, biodistribution and scintigraphy of 99mTc-paclitaxel: a potential tracer of paclitaxel. Journal of Radioanalytical and Nuclear Chemistry, 304, 633–643. [CrossRef]
• 23. Palestro, C. J., Love, C., Tomas, M. B. (2007). Infection and Inflammation. In: S. Treves (Ed.), Pediatric Nuclear Medicine/PET, (pp. 419–445). Springer, New York, NY. [CrossRef]
• 24. Rathmann, S. M., Ahmad, Z., Slikboer, S., Bilton, H. A., Snider, D. P., Valliant, J. F. (2019). The Radiopharmaceutical Chemistry of Technetium-99m. In: J. Lewis, A. Windhorst, B. Zeglis (Eds.), Radiopharmaceutical Chemistry, (pp. 311–333). Springer, Cham. [CrossRef]
• 25. O’Shaughnessy, J., Gradishar, W. J., Bhar, P., Iglesias, J. (2013). Nab-Paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: A retrospective analysis. Breast Cancer Research and Treatment, 138(3), 829–837. [CrossRef]
• 26. Fu, Q., Sun, J., Zhang, W., Sui, X., Yan, Z., He, Z. (2009). Nanoparticle albumin - bound (NAB) technology is a promising method for anti-cancer drug delivery. Recent Patents on Anti-Cancer Drug Discovery, 4(3), 262–272. [CrossRef]
• 27. Ten Tije, A. J., Verweij, J., Loos, W. J., Sparreboom, A. (2003). Pharmacological effects of formulation vehicles: Implications for cancer chemotherapy. Clinical Pharmacokinetics, 42(7), 665–685. [CrossRef]
• 28. Van Tellingen, O., Huizing, M. T., Nannan Panday, V. R., Schellens, J. H. M., Nooijen, W. J., Beijnen, J. H. (1999). Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. British Journal of Cancer, 81(2), 330–335. [CrossRef]
• 29. Sparreboom, A., Van Zuylen, L., Brouwer, E., Loos, W. J., De Bruijn, P., Gelderblom, H., Pillay, M., Nooter, K., Stoter, G., Verweij, J. (1999). Cremophor EL-mediated alteration of paclitaxel distribution in human blood: Clinical pharmacokinetic implications. Cancer Research, 59(7), 1454–1457.
• 30. Desai, N., Trieu, V., Damascelli, B., Soon-Shiong, P. (2009). SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Translational Oncology, 2(2), 59–64. [CrossRef]
• 31. Maeda, H., Wu, J., Sawa, T., Matsumura, Y., Hori, K. (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. Journal of Controlled Release, 65(1–2), 271–284. [CrossRef]
• 32. Ekinci, M., Santos-Oliveira, R., İlem-Özdemir, D. (2022). Biodistribution of 99mTc-PLA/PVA/Atezolizumab nanoparticles for non-small cell lung cancer diagnosis. European Journal of Pharmaceutics and Biopharmaceutics, 176, 21–31. [CrossRef]
• 33. Ekinci, M., Öztürk, A. A., Santos-Oliveira, R., İlem-Özdemir, D. (2022). The use of Lamivudine-loaded PLGA nanoparticles in the diagnosis of lung cancer: Preparation, characterization, radiolabeling with 99mTc and cell binding. Journal of Drug Delivery Science and Technology, 69, 103139. [CrossRef]
• 34. Ekinci, M., Ilem-Ozdemir, D., Gundogdu, E., Asikoglu, M. (2015). Methotrexate loaded chitosan nanoparticles: Preparation, radiolabeling and in vitro evaluation for breast cancer diagnosis. Journal of Drug Delivery Science and Technology, 30(A), 107–113. [CrossRef]
• 35. Maruvada, P., Wang, W., Wagner, P. D., Srivastava, S. (2005). Biomarkers in molecular medicine: cancer detection and diagnosis. BioTechniques, Suppl, 9–15. [CrossRef]
• 36. Monteiro, L. O. F., Fernandes, R. S., Oda, C. M. R., Lopes, S. C., Townsend, D. M., Cardoso, V. N., Oliveira, M. C., Leite, E. A., Rubello, D., de Barros, A. L. B. (2018). Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study. Biomedicine and Pharmacotherapy, 97, 489–495. [CrossRef]