Assessment of Hypoxia in Experimental Mice Tumours by [ 18 F] Fluoromisonidazole PET and pO 2 Electrode Measurements

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

“…Carbogen breathing decreased the 60-min tumour retention of [ 18 F]FETA by 36%, in keeping with an 11% decrease of hypoxic pO 2 values measured by OxyLite electrodes. This finding is similar to those reported previously for other 2-nitroimidazoles (Aboagye et al, 1997b(Aboagye et al, , 1998Rasey et al, 2000;Bentzen et al, 2002;Seddon et al, 2002) and demonstrates that [ 18 F]FETA can be used to detect acute changes in pO 2 .…”

“…This radiotracer has, however, failed to gain a wider acceptance for routine clinical application in a PET setting because of a number of limitations including: (i) slow accumulation in hypoxic tumours (scanning has been performed up to 5 h p.i. (Nunn et al, 1995;Bentzen et al, 2002)); (ii) low target-to-background contrast due to high nonspecific binding resulting from a relatively high lipophilicity (octanol/water partition coefficient ¼ 0.41 (Workman and Brown, 1981)); and (iii) significant non-oxygen-dependent metabolism (e.g. 50.0 and 36.2% of metabolites in plasma and urine, respectively, at 2 h p.i.…”

“…These include 18 F-labelled 2-nitroimidazoles such as [ 18 F]FMISO (Koh et al, 1995;Rasey et al, 1996), [ 18 F]EF5 (Ziemer et al, 2003), [ 18 F]FETNIM (Yang et al, 1995), [ 18 F]FAZA (Sorger et al, 2003), and N-(2-([ 18 F]fluoroethyl)-2-(2-nitroimidazol-1-yl)-acetamide ([ 18 F]FETA) (Rasey et al, 1999); copper bis-thiosemi-carbazones such as [ 60 Cu]ATSM (Fujibayashi et al, 1997;Dehdashti et al, 2003); technetium-based probes such as [ 99m Tc]HL-91 (Honess et al, 1998); and iodine-based probes such as [ 123 I]IAZA (Mannan et al, 1991). Due to various limitations, none of these radiotracers have found their way into routine clinical use (Workman and Brown, 1981;Nunn et al, 1995;Rasey et al, 1999;Bentzen et al, 2002).…”

Evaluation of hypoxia in an experimental rat tumour model by [18F]Fluoromisonidazole PET and immunohistochemistry

“…For all the tissues, cumulative histogram analysis was carried out. Bentzen et al (2002) found no correlation between [ 18 F]FMISO-PET and pO 2 electrode measurements in C3H mammary carcinomas. Piert et al (1999Piert et al ( , 2000 showed a correlation between [ 18 F]FMISO-PET data and pO 2 electrode measurements in a study of hypoxia in pig liver tissue.…”

“…Different studies have shown heterogeneity in, for example, larger C3H tumours growing subcutaneously in CDF1 mice and a more uniform radioactivity distribution in smaller C3H tumours (Bentzen et al, 2002;Grönroos et al, 2004). Tochon-Danguy et al (2002) observed only homogeneous distribution of [ 18 F]FMISO throughout C6 glioma tumours in the left brain of Wistar rats.…”