Evaluation of an oxygen-dependent degradable protein as a hypoxia-inducible factor-1-active tumor imaging agent

1909 Objectives Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional activator of various genes related to malignant phenotypes, and thus, the imaging of HIF-1-active tumors is important for targeting cancer therapy and predicting prognosis. We previously developed an oxygen-dependent degradable protein, POS, and succeeded in tumor imaging using 123I-labeled POS (123I-IPOS). In the present study, we aimed to demonstrate that the accumulation of radioiodinated POS reflects the expression of HIF-1. Methods The tumoral accumulation of 125I-IPOS was compared with HIF-1 activity using mice carrying tumors with the HIF-1-dependent luciferase reporter gene. The intratumoral distribution of 125I-IPOS was examined by autoradiography, and then the same sections were subjected to double-fluorescent immunostaining for pimonidazole (PIMO), which is a hypoxic marker, and HIF-1. Results 125I-IPOS was obtained with radiochemical yield of 65% and radiochemical purity of greater than 95%. The tumoral accumulation of 125I-IPOS was positively correlated with HIF-1 activity (R = 0.71,P Conclusions The accumulation of radioiodinated POS reflects the expression of HIF-1.