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Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α
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Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α
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Journal Article
Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α
2010
Overview
Purpose
Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-
123
I-iodobenzoyl)norbiotinamide (
123
I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and
123
I-IBB for rapid imaging of HIF-1-active tumours.
Methods
Tumour-implanted mice were pretargeted with POS. After 24 h,
125
I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between
125
I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of
125
I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1α immunohistochemistry.
Results
125
I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from
125
I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of
125
I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (
R
=0.84,
p
<0.01). The intratumoral distribution of
125
I-IBB was heterogeneous and was significantly correlated with HIF-1α-positive regions (
R
=0.58,
p
<0.0001).
Conclusion
POS pretargeting with
123
I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours.
Publisher
Springer-Verlag
Subject
