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J Nucl Med. 2008; 49 (Supplement 1):141P
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Radiopharmaceutical Chemistry: New Chemistry-Oncology

New Chemistry-Oncology III: Other

Pretargeting for tumor hypoxia imaging with an oxygen-degradable fusion protein by the same mechanism of hypoxia-inducible factor-1{alpha}

Takashi Kudo1, Masashi Ueda2, Hiroaki Konishi1, Yuji Kuge1, Shinae Kizaka-Kondoh3, Masahiro Hiraoka3 and Hideo Saji1

1 Department of Patho-Functional Bioanalysis, Kyoto University, Kyoto, Kyoto, Japan; 2 Radioisotopes Research Laboratory, Kyoto University Hospital, Kyoto, Kyoto, Japan; 3 Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Kyoto, Japan

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Objectives: HIF-1 is specifically degraded under normoxia and plays an important role in tumor progression under hypoxia. We previously reported the synthesis of the oxygen-dependent degradable protein, PCOS, and radioligand, 123/125I-IBB, which could bind to PCOS. In this study, we investigated the feasibility of 123I-IBB and PCOS for imaging tumor hypoxia using pretargeting method.

Methods: Biodistribution studies of 125I-IBB-conjugated PCOS (125I-IBB-PCOS) and 125I-IBB were performed in FM3A-implanted mice. Autoradiographic studies of 125I-IBB-PCOS in tumor were performed, and compared with pimonidazole immunostaining study for detecting hypoxic region. Furthermore, 24 h after pretargeting with PCOS, 125I-IBB was injected and its biodistribution was examined. Planar images were taken with [123I]IBB pretargeted with PCOS.

Results: The tumor accumulation of 125I-IBB-PCOS was 1.4 %ID/g and tumor/blood ratio was 5.1 at 24 h after injection. 125I-IBB-PCOS accumulated around the hypoxic regions in tumor. Using pretargeting method, the comparable radioactivity in tumor (1.6 %ID/g) and tumor/blood ratio (4.2) were obtained at only 6 h after injection. The tumoral uptake of 125I-IBB was decreased more than 50% by the injection of unlabeled IBB. Furthermore, tumor was visualized 6 h after injection of 123I-IBB in the pretargeting method.

Conclusions: PCOS distributed around hypoxic regions. The pretargeting method shortened the imaging time compared to the case of injection of 123I-IBB-PCOS. These results indicate PCOS pretargeting with 123I-IBB should be a potential procedure for tumor hypoxia imaging.





This Article
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Right arrow Articles by Kudo, T.
Right arrow Articles by Saji, H.
PubMed
Right arrow Articles by Kudo, T.
Right arrow Articles by Saji, H.