Trifluoromisonidazole Detects Hypoxia - An In Vivo & In Vitro Multimodality Study

Ellen Ackerstaff¹, Makiko Suehiro¹, Natalia Kruchevsky¹, Sean Carlin¹, Eric H. Rosenfeld¹, Paul Burgman¹, Guangbin Yang¹, Geralda Torchon¹, Ouathek Ouerfelli¹, Pat B. Zanzonico¹, Kristen L. Zakian¹, Clifton C. Ling¹, Jason A. Koutcher¹

Tumor hypoxia is related to treatment response and outcome. We evaluated the ability of trifluoromisonidazole (TFmiso) to detect hypoxia in vivo and in vitro. In vivo, TFmiso could reproducibly measure whole-tumor hypoxia and the effect of oxygenation changes (carbogen, oxygen breathing) on tumor hypoxia. Its accumulation in hypoxic tumor areas was validated ex vivo using ¹⁸F-TFmiso autoradiography and pimonidazole immunohistochemistry. In vitro, ¹⁸F-TFmiso is taken up preferentially at [O₂]<1% with the highest uptake in anoxic tumor cells and <50% of cellular TFmiso is protein bound. TFmiso imaging may be useful in identifying tumors that can be successfully reoxygenated and radiosensitized.