177Lutetium-Tedizolid for Imaging and Treatment of Infection

Yıl 2022, Cilt: 47 Sayı: 3, 369 - 380, 19.10.2022

Merve Karpuz , Emre Özgenç , Evren Gündoğdu , Zeynep Burak

https://doi.org/10.55262/fabadeczacilik.1099287

Öz

Infection is still one of the major health problems all around the world. Early diagnosis and differentiation of infection from other pathological conditions such as cancer and inflammation play a critical role in treating the infection in acute stages. Imaging techniques in the infection diagnosis present some advantages such as the ability to image the whole body, the detection of focal location and stage, and following up of infection. Although various antibiotics can be used in the treatment, there are some problems including serious side effects of antibiotics or the development of antimicrobial resistance in the clinics. In our study, tedizolid, a second-generation oxazolidinone antibiotic against gram-positive bacteria infections, was radiolabeled with 177Lu radionuclide to develop a theranostic agent for infection. The radiolabeling was performed under room conditions, and labeling efficiency and stability were evaluated by paper chromatography and HPLC. The optimum incubation period was found as 60 min to obtain high radiolabeling efficiency. Different mobile and stationary phases were tested for paper chromatography to determine the radiochemical impurities in 177Lu-TDZ solution, and ITLC-SG was found to be proper as the stationary phase. In addition, ammonium hydroxide: methanol: water and DTPA solutions were chosen as mobile phase. In the HPLC chromatogram, two different peaks were observed depending on retention times of the free 177Lu and 177Lu-TDZ complex. Unfortunately, over 80% purity values were not obtained in the results of radiolabeling stability analyses, therefore the addition of a chelating agent in the radiolabeling condition was suggested to increase the stability.

Anahtar Kelimeler

Lutetitum-177, tedizolid, theranostic

Destekleyen Kurum

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Proje Numarası

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Teşekkür

The authors wish to thank Assoc. Prof. Dr. Zeynep Şenyiğit for the generous gift of TDZ.

Enfeksiyon Görüntüleme ve Tedavisi için 177Lutesyum-Tedizolid

Öz

Enfeksiyon hastalıkları hala dünyada temel sağlık problemlerinden birini oluşturmaktadır. Enfeksiyonun erken aşamalarda teşhisi ve kanser veya inflamasyon gibi diğer patolojilerden ayrımı, enfeksiyonu akut aşamalarda tedavi etmede kritik rol oynamaktadır. Enfeksiyon teşhisinde kullanılan görüntüleme yöntemleri tüm vücut görüntüsü alabilme, enfeksiyonu odağını ve evresini tespit edebilme ve hastalığı izleyebilme gibi avantajlara sahiptir. Enfeksiyon tedavisinde çeşitli antibiyotikler kullanılmasına rağmen, klinikte antibiyotiklerin ciddi yan etkileri ve antimikrobiyal direnç gelişimi gibi problemler mevcuttur. Çalışmamızda enfeksiyon için teranostik bir ajan geliştirme amacıyla gram pozitif bakterilere karşı etkili ikinci nesil oksazolidinon antibiyotiği olan tedizolid, 177Lu radyonüklidi ile radyoişaretlenmiştir. Radyoiaşretleme, oda koşullarında gerçekleştirilmiş ve işaretleme etkinliği ile stabilitesi, kağıt kromatografisi ve HPLC ile değerlendirilmiştir. Yüksek radyoişaretleme verimi elde etmek için optimum inkübasyon süresi 60 dakika olarak bulunmuştur. 177Lu-TDZ çözeltisindeki radyokimyasal safsızlıkları belirleme amacıyla kağıt kromatografisi için farklı mobil ve sabit fazlar test edilmiş ve sabit faz olarak ITLC-SG uygun bulunmuştur. Ayrıca amonyum hidroksit: metanol: su ve DTPA çözeltileri mobil faz olarak seçilmiştir. HPLC kromatogramında serbest 177Lu ve 177Lu-TDZ kompleksinin alıkonma sürelerine bağlı olarak iki farklı pik gözlenmiştir. Ne yazık ki, radyoişaretleme stabilitesi testlerinin sonuçlarında %80'in üzerinde saflık değerleri elde edilememiştir, bu nedenle radyoişaretleme ortamına şelatla yapıcı ajan eklenmesi önerilmiştir.

Anahtar Kelimeler

Lutesyum-177, tedizolit, teranostik

Proje Numarası

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Kaynakça

• Aerts, J., Ballinger, J. R., Behe, M., Decristoforo, C., Elsinga, P. H., Faivre-Chauvet, A., . . . European Association of Nuclear, M. (2014). Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Comp Radiopharm, 57(10), 615-620. doi:10.1002/jlcr.3227
• Akbar, M. U., Bokhari, T. H., Khalid, M., Ahmad, M. R., Roohi, S., Hina, S., . . . Jabbar, T. (2017). Radiolabeling, quality control, and biological characterization of (177) Lu-labeled kanamycin. Chem Biol Drug Des, 90(3), 425-431. doi:10.1111/cbdd.12960
• Banerjee, S., Pillai, M. R., & Knapp, F. F. (2015). Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications. Chem Rev, 115(8), 2934-2974. doi:10.1021/cr500171e
• Banerjee, S., Pillai, M. R. A., & Knapp, F. F. (2015). Lutetium-177 Therapeutic Radiopharmaceuticals: Linking Chemistry, Radiochemistry, and Practical Applications. Chemical Reviews, 115(8), 2934-2974. doi:10.1021/cr500171e
• Bart, S. M., Rubin, D., Kim, P., Farley, J. J., & Nambiar, S. (2020). Trends in Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia Trials. Clinical Infectious Diseases, 73(3), e602-e608. doi:10.1093/cid/ciaa1712
• Breeman, W. A., De Jong, M., Visser, T. J., Erion, J. L., & Krenning, E. P. (2003). Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging, 30(6), 917-920. doi:10.1007/s00259-003-1142-0
• Bryant, A. E., Bayer, C. R., Aldape, M. J., McIndoo, E., & Stevens, D. L. (2020). Emerging erythromycin and clindamycin resistance in group A streptococci: Efficacy of linezolid and tedizolid in experimental necrotizing infection. J Glob Antimicrob Resist, 22, 601-607. doi:10.1016/j.jgar.2020.04.032 Cada, D. J., Ingram, K., & Baker, D. E. (2014). Tedizolid phosphate. Hosp Pharm, 49(10), 961-971. doi:10.1310/hpj4910-961
• de Blois, E., de Zanger, R. M. S., Chan, H. S., Konijnenberg, M., & Breeman, W. A. P. (2019). Radiochemical and analytical aspects of inter-institutional quality control measurements on radiopharmaceuticals. EJNMMI Radiopharm Chem, 4(1), 3. doi:10.1186/s41181-018-0052-1
• Gutfilen, B., Souza, S. A., & Valentini, G. (2018). Copper-64: a real theranostic agent. Drug Des Devel Ther, 12, 3235-3245. doi:10.2147/DDDT.S170879
• Hu, F., Cutler, C. S., Hoffman, T., Sieckman, G., Volkert, W. A., & Jurisson, S. S. (2002). Pm-149 DOTA bombesin analogs for potential radiotherapy: in vivo comparison with Sm-153 and Lu-177 labeled DO3A-amide-βAla-BBN(7–14)NH2. Nuclear Medicine and Biology, 29(4), 423-430. doi:https://doi.org/10.1016/S0969-8051(02)00290-1
• Jones, R. N. (2010). Microbial Etiologies of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia. Clinical Infectious Diseases, 51(Supplement_1), S81-S87. doi:10.1086/653053
• Kang, C. S., Chen, Y., Lee, H., Liu, D., Sun, X., Kweon, J., . . . Chong, H. S. (2015). Synthesis and evaluation of a new bifunctional NETA chelate for molecular targeted radiotherapy using(90)Y or(177)Lu. Nucl Med Biol, 42(3), 242-249. doi:10.1016/j.nucmedbio.2014.10.004
• Karpuz M., Ozgenc E., Atlihan-Gundogdu, E., Burak Z. (2022). Pre-study on radiolabeling of colistin with Lutetium-177 to develop theranostic infection agent. Journal of Research in Pharmacy, 26(2), 397-407. doi:http://dx.doi.org/10.29228/jrp.137
• Karpuz, M., & Silindir-Gunay, M. (2022). Lipid-Based Drug Delivery Systems and Their Role in Infection and Inflammation Imaging. In Nanoengineering of Biomaterials (pp. 469-503).
• Kassis, A. I. (2008). Therapeutic radionuclides: biophysical and radiobiologic principles. Semin Nucl Med, 38(5), 358-366. doi:10.1053/j.semnuclmed.2008.05.002
• Klähn, M., Mathias, G., Kötting, C., Nonella, M., Schlitter, J., Gerwert, K., & Tavan, P. (2004). IR Spectra of Phosphate Ions in Aqueous Solution:  Predictions of a DFT/MM Approach Compared with Observations. The Journal of Physical Chemistry A, 108(29), 6186-6194. doi:10.1021/jp048617g
• Levine, R., & Krenning, E. P. (2017). Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine. J Nucl Med, 58(Suppl 2), 3S-9S. doi:10.2967/jnumed.116.186502
• Liu, C., Bayer, A., Cosgrove, S. E., Daum, R. S., Fridkin, S. K., Gorwitz, R. J., . . . Infectious Diseases Society of, A. (2011). Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis, 52(3), e18-55. doi:10.1093/cid/ciq146
• Michalska, K., Mizera, M., Lewandowska, K., & Cielecka-Piontek, J. (2016). Infrared, Raman and ultraviolet with circular dichroism analysis and theoretical calculations of tedizolid. Journal of Molecular Structure, 1115, 136-143. doi:https://doi.org/10.1016/j.molstruc.2016.02.098
• Mota, F., Jadhav, R., Ruiz-Bedoya, C. A., Ordonez, A. A., Klunk, M. H., Freundlich, J. S., & Jain, S. K. (2020). Radiosynthesis and Biodistribution of (18)F-Linezolid in Mycobacterium tuberculosis-Infected Mice Using Positron Emission Tomography. ACS Infect Dis, 6(5), 916-921. doi:10.1021/acsinfecdis.9b00473 Mulcahy, M. E., & McLoughlin, R. M. (2016). Staphylococcus aureus and Influenza A Virus: Partners in Coinfection. mBio, 7(6). doi:10.1128/mBio.02068-16
• Naqvi, S. A. R., Rasheed, R., Ahmed, M. T., Zahoor, A. F., Khalid, M., & Mahmood, S. (2017). Radiosynthesis and preclinical studies of 177Lu-labeled sulfadiazine: a possible theranostic agent for deep-seated bacterial infection. Journal of Radioanalytical and Nuclear Chemistry, 314(2), 1023-1029. doi:10.1007/s10967-017-5477-6
• Paczkowska-Walendowska, M., Rosiak, N., Tykarska, E., Michalska, K., Plazinska, A., Plazinski, W., . . . Cielecka-Piontek, J. (2020). Tedizolid-Cyclodextrin System as Delayed-Release Drug Delivery with Antibacterial Activity. Int J Mol Sci, 22(1). doi:10.3390/ijms22010115
• Shahzad, M. A., Naqvi, S. A. R., Rasheed, R., Yameen, M., Anjum, F., Ahmed, M. T., . . . Gillani, S. J. H. (2017). Radiolabeling of benzylpenicillin with lutetium-177: Quality control and biodistribution study to develop theranostic infection imaging agent. Pak J Pharm Sci, 30(6(Supplementary)), 2349-2354.
• Singh, V., Upadhyay, P., Reddy, J., & Granger, J. (2021). SARS-CoV-2 respiratory co-infections: Incidence of viral and bacterial co-pathogens. Int J Infect Dis, 105, 617-620. doi:10.1016/j.ijid.2021.02.087
• Srivastava, S., Cirrincione, K. N., Deshpande, D., & Gumbo, T. (2020). Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis. Front Pharmacol, 11, 616294. doi:10.3389/fphar.2020.616294
• Tong, S. Y., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G., Jr. (2015). Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev, 28(3), 603-661. doi:10.1128/CMR.00134-14
• Velikyan, I. (2014). Chapter 17 - Radionuclides for Imaging and Therapy in Oncology. In X. Chen & S. Wong (Eds.), Cancer Theranostics (pp. 285-325). Oxford: Academic Press.
• Watanabe, S., Hashimoto, K., & Ishioka, N. S. (2015). Lutetium-177 complexation of DOTA and DTPA in the presence of competing metals. Journal of Radioanalytical and Nuclear Chemistry, 303(2), 1519-1521. doi:10.1007/s10967-014-3590-3
• Wu, M., & Shu, J. (2018). Multimodal Molecular Imaging: Current Status and Future Directions. Contrast Media Mol Imaging, 2018, 1382183. doi:10.1155/2018/1382183
• Wunderink, R. G., Roquilly, A., Croce, M., Rodriguez Gonzalez, D., Fujimi, S., Butterton, J. R., . . . De Anda, C. (2021). A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia. Clin Infect Dis, 73(3), e710-e718. doi:10.1093/cid/ciab032
• Xu, Q., Zhang, S., Zhao, Y., Feng, Y., Liu, L., Cai, L., . . . Chen, Y. (2019). Radiolabeling, quality control, biodistribution, and imaging studies of (177) Lu-ibandronate. J Labelled Comp Radiopharm, 62(1), 43-51. doi:10.1002/jlcr.3694
• Yang, Z., Tian, L., Liu, J., & Huang, G. (2018). Construction and evaluation in vitro and in vivo of tedizolid phosphate loaded cationic liposomes. J Liposome Res, 28(4), 322-330. doi:10.1080/08982104.2017.1380665
• Yousefnia, H., Jalilian, A. R., Zolghadri, S., Bahrami-Samani, A., Shirvani-Arani, S., & Ghannadi-Maragheh, M. (2010a). Preparation and quality control of (1)(7)(7)Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy. Nucl Med Rev Cent East Eur, 13(2), 49-54. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21598226
• Yousefnia, H., Jalilian, A. R., Zolghadri, S., Bahrami-Samani, A., Shirvani-Arani, S., & Ghannadi-Maragheh, M. (2010b). Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent. Nukleonika, 55(3), 285-291.