Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice

Cancer Science
Huizi Keiko LiSumitaka Hasegawa

Abstract

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 (211 At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that 211 At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with 211 At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211 At-trastuzumab (1 MBq) was a more efficient means of delivery of 211 At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211 At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by ind...Continue Reading

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Citations

Dec 21, 2018·Nihon Hoshasen Gijutsu Gakkai zasshi·Kohei HanaokaHiroyuki Tsushima
Jun 20, 2020·Cancer Biotherapy & Radiopharmaceuticals·Francisco D C Guerra LiberalKevin M Prise
Feb 24, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tadashi WatabeJun Hatazawa
Oct 7, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Satoshi KodairaSumitaka Hasegawa
Jun 4, 2021·Bioorganic & Medicinal Chemistry·Katsumasa Fujiki, Katsunori Tanaka
Jun 22, 2021·ACS Omega·Shino ManabeYasuhiro Matsumura
Jul 3, 2021·Pharmaceutics·Romain EychenneJean-François Gestin
Feb 7, 2021·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Huizi Keiko LiSumitaka Hasegawa

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Methods Mentioned

BETA
surgical resection
dissection
xenograft
xenografts
bioluminescence imaging

Software Mentioned

Bio
1D
Statcel
JMP

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