In vivo visualization of heterogeneous intratumoral distribution of hypoxia-inducible factor-1α activity by the fusion of high-resolution SPECT and morphological imaging tests.
OBJECTIVE
We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α (HIF) activity in tumor tissues in vivo.


METHODS
We synthesized of (125)I-IPOS, a (125)I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of (125)I-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 (125)I-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
(125)I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of (125)I-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 (125)I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of (125)I-IPOS.


CONCLUSIONS
High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of (125)I-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.
Functional Imaging Division, National Cancer Center Hospital East, Kashiwa 277-8577, Japan.
Hirofumi
H
Fujii
Masayuki
M
Yamaguchi
Kazumasa
K
Inoue
Yasuko
Y
Mutou
Masashi
M
Ueda
Hideo
H
Saji
Shinae
S
Kizaka-Kondoh
Noriyuki
N
Moriyama
Izumi O
IO
Umeda
D000818:Animals; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000493:pharmacokinetics*; D009374:Neoplasms, Experimental / Q000378:metabolism; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007457:Iodine Radioisotopes; D015335:Molecular Probes; D009593:Nitroimidazoles; C033815:pimonidazole