In Vivo Visualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1α Activity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests

Abstract EN

Purpose.

We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α (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.