The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3

Yoichi Takakusagi; Aya Sugyo; Atsushi B Tsuji; Hitomi Sudo; Masahiro Yasunaga; Yasuhiro Matsumura; Fumio Sugawara; Kengo Sakaguchi; Tatsuya Higashi

doi:10.1016/j.tranon.2021.101285

The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3

Transl Oncol. 2022 Jan;15(1):101285. doi: 10.1016/j.tranon.2021.101285. Epub 2021 Nov 25.

Authors

Yoichi Takakusagi¹, Aya Sugyo², Atsushi B Tsuji³, Hitomi Sudo², Masahiro Yasunaga⁴, Yasuhiro Matsumura⁵, Fumio Sugawara⁶, Kengo Sakaguchi⁶, Tatsuya Higashi²

Affiliations

¹ Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), 4-9-1 Inage, Chiba 263-8555, Japan; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQLS), 4-9-1 Inage, Chiba 263-8555, Japan.
² Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), 4-9-1 Inage, Chiba 263-8555, Japan.
³ Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), 4-9-1 Inage, Chiba 263-8555, Japan. Electronic address: tsuji.atsushi@qst.go.jp.
⁴ Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
⁵ Department of Immune Medicine, National Cancer Center Research Institute 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
⁶ pplied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Malignant Tumor Treatment Technologies (M.T.3) Inc., 3-20-2 Shibaura, Minato-ku, Tokyo 108-0023, Japan.

Abstract

α-Sulfoquinovosylacyl-1,3-propanediol (SQAP) is a semi-synthetic derivative of natural sulfoglycolipid that sensitizes tumors to external-beam radiotherapy. How SQAP affects internal radiotherapy, however, is not known. Here, we investigated the effects of SQAP for radioimmunotherapy (RIT) targeting tissue factor (TF) in a stroma-rich refractory pancreatic cancer mouse model, BxPC-3. A low dose of SQAP (2 mg/kg) increased tumor uptake of the ¹¹¹In-labeled anti-TF antibody 1849, indicating increased tumor perfusion. The addition of SQAP enhanced the growth-inhibitory effect of ⁹⁰Y-labeled 1849 without leading to severe body weight changes, allowing for the dose of ⁹⁰Y-labeled 1849 to be reduced to half that when used alone. Histologic analysis revealed few necrotic and apoptotic cells, but Ki-67-positive proliferating cells and increased vascular formation were detected. These results suggest that the addition of a low dose of SQAP may improve the therapeutic efficacy of TF-targeted RIT by increasing tumor perfusion, even for stroma-rich refractory pancreatic cancer.

Keywords: Molecular radiotherapy; Neoangiogenesis; Radionuclide; Refractory cancer; Therapeutic nuclear medicine.