How to Modulate Tumor Hypoxia for Preclinical In Vivo Imaging Research

Figure 4

Hypoxia-pretreatment experiment, approved by the Antwerp University Ethical Committee (2012-69). All applicable institutional and European guidelines for animal care and use were followed. (a) Colo205 cells (Perkin Elmer) were exposed to hypoxia (0-1% O₂) for 72 h in a Bactron IV Anaerobic Chamber (Shell Lab) or to normoxia (21% O₂) in a common incubator. CD-1 nude mice (Charles River, ) were inoculated with 2 × 10⁶ “hypoxic” cells in the shoulder and with 2 × 10⁶ “normoxic” cells in the hind leg. Fourteen days later, animals underwent a [¹⁸F]FMISO PET/CT scan as previously described [53]. Images were analyzed as previously described [53]. One representative mouse is shown. Arrows indicate tumors. As [¹⁸F]FMISO clearance mainly occurs via the hepatobilary pathway and the gastrointestinal tract [8], tracer uptake can be observed in liver and intestines. (b) “Hypoxic” tumors were numerically, but not significantly, smaller than “normoxic” tumors (144 ± 129 mm³ vs 328 ± 158 mm³ [mean ± SEM], respectively; ). (c) [¹⁸F]FMISO SUV did not differ between “hypoxic” and “normoxic” tumors (0.228 ± 0.074 vs 0.195 ± 0.090, respectively; ).

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