177Lutetium-Tedizolid for Imaging and Treatment of Infection

Year 2022, Volume: 47 Issue: 3, 369 - 380, 19.10.2022

Merve Karpuz , Emre Özgenç , Evren Gündoğdu , Zeynep Burak

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

Abstract

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.

Keywords

Lutetitum-177, tedizolid, theranostic

Supporting Institution

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Project Number

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Thanks

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

Enfeksiyon Görüntüleme ve Tedavisi için 177Lutesyum-Tedizolid

Abstract

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.

Keywords

Lutesyum-177, tedizolit, teranostik

Project Number

-

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