Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside

Morand Piert, Hans Jürgen Machulla, Maria Picchio, Gerald Reischl, Sybille Ziegler, Piyush Kumar, Hans Jürgen Wester, Roswitha Beck, Alexander J B McEwan, Leonard I. Wiebe, Markus Schwaiger

Research output: Contribution to journalArticle

Abstract

The study was performed to compare the 18F-labeled nitroimidazole compound fluoroazomycin arabinoside (18F-FAZA) with the standard hypoxia tracer fluoromisonidazole (18F-FMISO) in detection of tumor tissue hypoxia and to verify the oxygenation dependency of 18F-FAZA uptake. Methods: Biodistribution of 18F-FAZA was studied at various time points in EMT6 tumor-bearing BALB/c mice and in AR42J and A431 tumor-bearing nude mice and compared with that of 18F-FMISO. The presence of tumor tissue hypoxia was verified in 5 EMT6 and 5 AR42J tumors using an oxygen-sensing needle electrode system. To evaluate the oxygenation dependency of 18F-FAZA uptake, using the Munich prototype animal PET scanner, 2 serial PET scans were performed in 13 A431 tumor-bearing nude mice breathing pure oxygen or room air on 1 d and then selecting the other oxygen breathing condition on the following day. In addition, digital autoradiography was performed with EMT6 tumor-bearing 18F-FAZA-dosed, nude mice breathing either room air (n = 8) or carbogen (n = 9). Results: Tissue partial pressure of oxygen (Po2) electrode measurements revealed that tumor hypoxia was present under room air breathing in EMT6 (tissue Po2 = 2.9 ± 2.6) and AR42J tumors (tissue Po2 = 0.4 ± 0.2), which was significantly lower compared with that of reference tissue (tissue Po2 = 25.8 ± 6.7 and tissue Po2 = 29.0 ± 3.0 [mean ± SD], respectively; P <0.01). In all tumor models, 18F-FAZA displayed significantly higher tumor-to-muscle and tumor-to-blood ratios compared with 18F-FMISO, indicating a faster clearance of 18F-FAZA from normal tissues. In AR42J tumors, 18F-FAZA tumor-to-normal ratios were found to increase over time. Serial animal 18F-FAZA PET studies showed that the tumor-to-background ratio was significantly higher in animals breathing room air compared with that of animals breathing pure oxygen (7.3 ± 2.3 vs. 4.2 ± 1.2, respectively; P <0.001). Similarly, autoradiography showed significantly higher tumor-to-muscle ratios in mice breathing room air compared with those of animals breathing carbogen (5.3 ± 0.8 vs. 2.2 ± 0.8; respectively; P <0.02). Conclusion: 18F-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. This study also verified a hypoxia-specific up-take mechanism for 18F-FAZA in murine tumor models.

Original languageEnglish
Pages (from-to)106-113
Number of pages8
JournalJournal of Nuclear Medicine
Volume46
Issue number1
Publication statusPublished - 2005

Keywords

  • F-fluoroazomycin arabinoside
  • Mouse tumor model
  • PET tracers
  • Tumor hypoxia

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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    Piert, M., Machulla, H. J., Picchio, M., Reischl, G., Ziegler, S., Kumar, P., Wester, H. J., Beck, R., McEwan, A. J. B., Wiebe, L. I., & Schwaiger, M. (2005). Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. Journal of Nuclear Medicine, 46(1), 106-113.