Noninvasive assessment of tumor hypoxia with 99mTc labeled metronidazole

Yang D. J., ILGAN S., Higuchi T., Zareneyrizi F., Oh C., Liu C., ...Daha Fazla

Pharmaceutical Research, cilt.16, sa.5, ss.743-750, 1999 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 5
  • Basım Tarihi: 1999
  • Doi Numarası: 10.1023/a:1018836911013
  • Dergi Adı: Pharmaceutical Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.743-750
  • Anahtar Kelimeler: 99mTc, Imaging, Metronidazole, Radiosensitizer, Tumor hypoxia
  • Maltepe Üniversitesi Adresli: Hayır

Özet

Purpose. The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a 99mTc-labeled metronidazole (MN) using ethylenedicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. Methods. EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of 99mTc-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole- body autoradiograms were performed. The data was compared to that using 99mTc-EC (control), [18F]fluoromisonidazole (FMISO) and [131I] iodomisonidazole (IMISO). Results. In vivo biodistribution of 99mTc-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to- muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with 99mTc-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99m)Tc-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between 99mTc-EC-MN and [131I]IMISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both 969mTc-EC-MN and [131I]IMISO have higher tumor-to-muscle ratios compared to [18]FMISO. Conclusions. It is feasible to use 99mTc-EC-MN to image tumor hypoxia.