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

Ogawa, Kazuma*; Mukai, Takahiro*; Kawai, Keiichi*; Takamura, Norito*; Hanaoka, Hirofumi*; Hashimoto, Kazuyuki; Shiba, Kazuhiro*; Mori, Hirofumi*; Saji, Hideo*

European Journal of Nuclear Medicine and Molecular Imaging, 36(1), p.115 - 121, 2009/01

https://doi.org/10.1007/s00259-008-0925-8

We have developed a Re-MAG3 complex-conjugated bisphosphonate (Re-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 Re-MAG3-HBP because it has been reported that the concurrent administration of Tc-MAG3 and drugs with high affinity for serum protein enhanced total clearance and tissue distribution. The protein binding of Re-MAG3-HBP in a human serum albumin solution was significantly decreased by the addition of ceftriaxone. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. 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.