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European Journal of Nuclear Medicine and Molecular Imaging
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 1/2009

01.01.2009 | Original Article

Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an agent for treatment of painful bone metastases

verfasst von: Kazuma Ogawa, Takahiro Mukai, Keiichi Kawai, Norito Takamura, Hirofumi Hanaoka, Kazuyuki Hashimoto, Kazuhiro Shiba, Hirofumi Mori, Hideo Saji

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 1/2009

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Abstract

Purpose

We have developed a 186Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate (186Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of 186Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of 99mTc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution.

Methods

The displacement effects of several protein-binding inhibitors on the protein binding of 186Re-MAG3-HBP were investigated. Biodistribution experiments were performed by intravenously administering 186Re-MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or saline.

Results

The protein binding of 186Re-MAG3-HBP in rat serum, human serum, and a human serum albumin solution was significantly decreased by the addition of ceftriaxone, which has high affinity for binding site I on serum albumin. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of 186Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone.

Conclusions

The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein.
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Metadaten
Titel
Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an agent for treatment of painful bone metastases
verfasst von
Kazuma Ogawa
Takahiro Mukai
Keiichi Kawai
Norito Takamura
Hirofumi Hanaoka
Kazuyuki Hashimoto
Kazuhiro Shiba
Hirofumi Mori
Hideo Saji
Publikationsdatum
01.01.2009
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 1/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0925-8

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