In vivo visualization of heterogeneous intratumoral distribution of hypoxia-inducible factor-1α activity by the fusion of high-resolution SPECT and morphological imaging tests

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1 (HIF) activity in tumor tissues in vivo. Methods. We synthesized of ¹²⁵I-IPOS, a ¹²⁵I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of ¹²⁵I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of ¹²⁵I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtained in vivo SPECT-CT fusion images were compared with ex vivo images of excised tumors. Fusion imaging with MRI was also examined. Results. ¹²⁵I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of ¹²⁵I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of ¹²⁵I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of ¹²⁵I-IPOS. Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of ¹²⁵I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activity in vivo.