Biodistribution of Gadolinium Incorporated in Lipid Emulsions Intraperitoneally Administered for Neutron-Capture Therapy with Tumor-Bearing Hamsters

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概要

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• Emulsions containing a distearylamide (Gd-DTPA-SA) or a distearylester (Gd-DTPA-SE) of Gd (gadolinium)-diethylenetriaminepentaacetic acid (Gd-DTPA) were intraperitoneally injected in Greene's melanomabearing hamsters at a dose of 2.0 ml (3.0 or 6.0 mg Gd) per hamster. In the standard-Gd and high-Gd formulations used, the weight ratios of soybean oil, water, Gd-DTPA derivative (Gd-DTPA-SA or Gd-DTPA-SE), hydrogenated L-α-phosphatidylcholine from egg yolk (HEPC) and co-surfactant (HCO-60,Myrj 53,Myrj 59 or Brij 700) were 7.36 : 92 : 1 : 2 : 3 and 7.36 : 92 : 2 : 1 : 3,respectively. When the effects of the co-surfactants on the biodistribution of Gd from Gd-DTPA-SA-containing emulsions in the standard-Gd formulation were compared, the HCO-60 emulsion exhibited the highest Gd accumulation in tumors, possibly resulting from its fast and complete absorption, its small particle size (78nm) and the stable coat on the particle surfaces with polyoxyethylene. Brij 700 emulsion kept the highest blood Gd concentration for a prolonged period, possibly due to particle properties similar to those of HCO-60. However, it exhibited a slower Gd accumulation in tumors, only reaching an identical level, in comparison with the HCO-60 emulsion. This suggested the tumor to be saturated with lipid particles. When Gd-DTPA-SE was used instead of Gd-DTPA-SA, its HCO-60 emulsion exhibited only very poor Gd-accumulation due to its easy degradation. The HCO-60 emulsion particles containing Gd-DTPA-SA in the high-Gd formulation (6.0 mg Gd in 2 ml) exhibited in vivo behavior identical to those in the standard-Gd formulation; then the Gd level in tumors reached 107 μg Gd/g tumor (wet), and the tumor : blood (T/B) and tumor : skin (T/Sk) Gd concentration ratios were 13.2 and 5.6,respectively, at 48 h after intraperitoneal administration. These results suggest that when intraperitoneally administered, this HCO-60 emulsion, and possibly also the corresponding Brij 700 emulsion, may be an excellent delivery system for accumulating Gd in tumors in neutroncapture therapy (NCT).

• 公益社団法人日本薬学会の論文
• 1999-12-15

著者

• 市川 秀喜

  神戸学院大学薬学部

• 市川 秀喜

  神戸学院大学薬学部物性薬学部門製剤学研究室 同ライフサイエンス産学連携研究センター

• Hirano Kaoru

  Faculty Of Pharmaceutical Sciences Kobe Gakuin University

• AKINE Yasuyuki

  Institute of Clinical Medicine,University of Tsukuba

• Akine Y

  Institute Of Clinical Medicine University Of Tsukuba

• Akine Yasuyuki

  Institute Of Clinical Medicine University Of Tsukuba

• MIYAMOTO Mitsue

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• FUKUMORI Yoshinobu

  Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• 福森 義信

  神戸学院大学 薬学部

• Fukumori Yoshinobu

  Faculty Of Pharmaceutical Sciences Kobe-gakuin University

• Fukumori Yoshinobu

  Faculty Of Pharmaceutical Science Kobe Gakuin University

• ICHIKAWA Hideki

  Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin Uni

• Ichikawa Hideki

  Department Of Physical Pharmacy Kobe Gakuin University

• Ichikawa Hideki

  Faculty Of Pharmaceutical Science Kobe Gakuin University

• Tokuuye Koichi

  Department Of Radiation Therapy The National Cancer Hospital

• MIYAMOTO Masahito

  Faculty of Pharmaceutical Sciences, Kobe Gakuin University

• TOKUUYE Koichi

  The National Cancer Center Hospital

• Miyamoto Masahito

  Faculty Of Pharmaceutical Sciences Kobe Gakuin University

• Fukumori Yoshinobu

  Department Of Physical Pharmacy Kobe Gakuin University

• Miyamoto M

  Department Of Biochemistry Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And App

• Hirano K

  Kyoto Pharmaceutical University

• Miyamoto M

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

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