In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography.

Abstract

Development of hypoxia-targeted therapies has stimulated the search for clinically applicable noninvasive markers of tumour hypoxia. Here, we describe the validation of [(18)F]fluoroetanidazole ([(18)F]FETA) as a tumour hypoxia marker by positron emission tomography (PET). Cellular transport and retention of [(18)F]FETA were determined in vitro under air vs nitrogen. Biodistribution and metabolism of the radiotracer were determined in mice bearing MCF-7, RIF-1, EMT6, HT1080/26.6, and HT1080/1-3C xenografts. Dynamic PET imaging was performed on a dedicated small animal scanner. [(18)F]FETA, with an octanol-water partition coefficient of 0.16+/-0.01, was selectively retained by RIF-1 cells under hypoxia compared to air (3.4- to 4.3-fold at 60-120 min). The radiotracer was stable in the plasma and distributed well to all the tissues studied. The 60-min tumour/muscle ratios positively correlated with the percentage of pO(2) values <5 mmHg (r=0.805, P=0.027) and carbogen breathing decreased [(18)F]FETA-derived radioactivity levels (P=0.028). In contrast, nitroreductase activity did not influence accumulation. Tumours were sufficiently visualised by PET imaging within 30-60 min. Higher fractional retention of [(18)F]FETA in HT1080/1-3C vs HT1080/26.6 tumours determined by dynamic PET imaging (P=0.05) reflected higher percentage of pO(2) values <1 mmHg (P=0.023), lower vessel density (P=0.026), and higher radiobiological hypoxic fraction (P=0.008) of the HT1080/1-3C tumours. In conclusion, [(18)F]FETA shows hypoxia-dependent tumour retention and is, thus, a promising PET marker that warrants clinical evaluation.

• Authors: H Barthel, H Wilson, D R Collingridge, G Brown, S Osman, S K Luthra, F Brady, P Workman, P M Price, E O Aboagye
• Journal: British journal of cancer (Br J Cancer) Vol. 90 Issue 11 Pg. 2232-42 (Jun 01 2004) ISSN: 0007-0920 [Print] England
• PMID: 15150578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• fluoroetanidazole
• Etanidazole

Topics

• Animals
• Breast Neoplasms (diagnostic imaging)
• Cell Hypoxia
• Etanidazole (analogs & derivatives, pharmacokinetics)
• Fibrosarcoma (diagnostic imaging)
• Fluorine Radioisotopes (pharmacokinetics)
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental
• Tomography, Emission-Computed
• Transplantation, Heterologous