Pharmaceutical Research

, Volume 16, Issue 5, pp 743–750

Noninvasive Assessment of Tumor Hypoxia with 99mTc Labeled Metronidazole

  • David J. Yang
  • Seyfettin Ilgan
  • Tetsuya Higuchi
  • Fereshteh Zareneyrizi
  • Chang-Sok Oh
  • Chun-Wei Liu
  • E. Edmund Kim
  • Donald A. Podoloff
Article

DOI: 10.1023/A:1018836911013

Cite this article as:
Yang, D.J., Ilgan, S., Higuchi, T. et al. Pharm Res (1999) 16: 743. doi:10.1023/A:1018836911013

Abstract

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 ethylene-dicysteine (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 l-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), [l8F]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 99mTc-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 99mTc-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.

metronidazole99mTctumor hypoxiaimagingradiosensitizer

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • David J. Yang
    • 1
  • Seyfettin Ilgan
    • 1
  • Tetsuya Higuchi
    • 1
  • Fereshteh Zareneyrizi
    • 1
  • Chang-Sok Oh
    • 1
  • Chun-Wei Liu
    • 1
  • E. Edmund Kim
    • 1
  • Donald A. Podoloff
    • 1
  1. 1.Department of Nuclear MedicineThe University of Texas M. D. Anderson Cancer CenterHouston