PET imaging of tumor hypoxia using ¹⁸F-labeled pimonidazole

Figures & data

Figure 1. [¹⁸F]FPIMO synthesis overview showing the molecular structure of the tosylated precursor and the two resulting ¹⁸F-labeled, spontaneously convertible, isomers named “5” and “6”.

Figure 2. Head-to-head comparison of [¹⁸F]FPIMO (isomer “5”) and [¹⁸F]FAZA in two different murine tumor models (C3H and SCCVII) measured 3 hours following administration of tracer (A–C). For comparison, also tumor-to-reference tissue values obtained for isomer “6” in SCCVII tumors at various sampling time points, are included (D). In the C3H model (A), tumor-to-reference tissue ratios were significantly higher for [¹⁸F]FAZA than for [¹⁸F]FPIMO, whereas no significant difference was observed in the SCCVII tumor model (B). In both tumor models, SUV values were significantly lower for [¹⁸F]FPIMO than for [¹⁸F]FAZA (C). The corresponding autoradiograms and pimonidazole stainings show that both [¹⁸F]FPIMO and [¹⁸F]FAZA is retained in hypoxic tumor areas, but intra-tumoral contrast is somewhat better for [¹⁸F]FAZA in the C3H tumor (less [¹⁸F]FAZA signal in non-hypoxic viable tissue despite similar signal for the two tracers in hypoxic areas). Values are means ± SEM. n ≥ 3. *Denotes a significant difference between [¹⁸F]FPIMO and [¹⁸F]FAZA (p < 0.05).

Figure 3. [¹⁸F]FPIMO biodistribution data for tumor-bearing mice obtained at different post-injection times. Biodistribution of isomer “5” obtained in C3H/HeNHsd mice bearing SCCVII tumors. Upper left panel shows data for isomer “5” and upper right panel shows data for isomer “6”. The sagittal-view PET images shows a direct comparison of [¹⁸F]FAZA and [¹⁸F]FPIMO in mice bearing tumors at their lower backs (white arrows shows the tumor position). Images were obtained 3 hours following tracer administration. Values are means ± SEM. n = 4 for isomer “5” and n = 5 for isomer “6”.