Hasan DEMİROĞLU, Gökçen TOPAL, Yasemin PARLAK, Fikriye Gül GÜMÜŞER, Elgin ULUER TÜRKÖZ, Volkan TEKİN, Buket ATEŞ, PERİHAN ÜNAK, UĞUR AVCIBAŞI

Radiosynthesis and Biodistribution of 99mTc-Trimethoprim: A Novel Radiolabeled Antibiotic for Bacterial Infection Imaging Using Experimental Animals

In the present article, we focused on the radiolabeling and evaluation of 99mTc–TMH complex as a potential candidate for infection imaging in vivo. For this; Trimethoprim (TMH) used to treat bacterial infections was investigated to label with 99mTc. Labeling was performed using thin (II) chloride as a reducing agent at room temperature for 1 h and radiochemical analysis involved thin layer radiochromatography (TLRC) and high pressure liquid radiochromatograpy (HPLRC) methods. The stability of labeled antibiotic was checked in the presence of rat blood serum at 37ºC up to 180 min. The maximum radiolabeling yield was found to be 96±2% and remained constant at more than 85±1% even in rat serum for 180 min after radiolabeling. Static image of 99mTc-TMH in male rats demonstrated that important radiation signals are present in the infected site at first glance in 30 min. After 30 min the uptake of the 99mTc-TMH as ID/g% in the infected muscle (INM) and normal muscle (NM) of the rats were 7.5±1.5% and 5.00±1.2%, respectively. In the INM/NM ratio a desirable behavior was observed as the values for the INM/ NM increased up to 10.6. 99mTc-TMH prepared with high yield is able to localize well in the bacterially infected muscle of the rats. As a result, 99mTc-TMH may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging.

99mTc-Trimethoprim’in Radyosentezi ve Biyodağılımı: Deney Hayvanları Kullanılarak Bakteriyel Enfeksiyon Görüntüleme İçin Yeni Bir Radyoişaretli Antibiyotik

Bu çalışmada in vivo enfeksiyon görüntüleme için potansiyel bir aday olarak 99mTc-TMH’ı değerlendirdik ve radyosentezi üzerine odaklandık. Bunun için bakterilerden kaynaklı enfeksiyonların tedavisinde kullanılan Trimethoprim (TMH) 99mTc ile işaretlenmiştir. İşaretlenme oda sıcaklığında 1 saat süreyle bir indirgenme ajanı olan Sn(II)Cl2 kullanılarak gerçekleştirilmiş ve ince tabaka radyokromatografi (TLRC) ve yüksek basınçlı sıvı radyokromatografisi (HPLRC) metodlarını içeren radyokimyasal analizler yapılmıştır. İşaretli antibiyotiğin sıçan kan serumundaki kararlılığı 37ºC’de 180. dk.’ya kadar kontrol edilmiştir. Maksimum bağlanma verimi %96±2 olarak bulunmuş ve işaretli antibiyotiğin işaretlenmeden sonra 180 dk süresi içinde sıçan serumunda %85±1’in üzerindeki bir oranda sabit kaldığı görülmüştür. Dişi sıçanlardaki 99mTcTMH’ın statik görüntüsü ilk 30 dk içinde enfeksiyon bölgesinde işaretli antibiyotiğin önemli bir radyasyon sinyali verdiğini göstermiştir. 30 dk sonra 99mTc-TMH’ın enfekte kas (INM) ve normal kas (NM) daki tutulum değerleri sırasıyla %7.5±1.5 ve %5.00±1.2 dir. INM/NM oranı 10.6 değerine kadar attığı için INM/NM oranında makul bir artış gözlenmiştir. Yüksek verimle hazırlanmış 99mTc-TMH bakteriler tarfından enfekte edilmiş sıçan kaslarında lokalize olabilmektedir. Sonuç olarak 99mTc-TMH nükleer görüntülemede kullanılabilecek bir radyofarmasötik olarak geliştirilebilir.

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