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

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...

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Autores principales:	Yoichi Takakusagi, Aya Sugyo, Atsushi B. Tsuji, Hitomi Sudo, Masahiro Yasunaga, Yasuhiro Matsumura, Fumio Sugawara, Kengo Sakaguchi, Tatsuya Higashi
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Refractory cancer Molecular radiotherapy Therapeutic nuclear medicine Radionuclide Neoangiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/47bda2ddaee24e27979c80f2bea5f435
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spelling	oai:doaj.org-article:47bda2ddaee24e27979c80f2bea5f4352021-11-26T04:26:37ZThe natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-31936-523310.1016/j.tranon.2021.101285https://doaj.org/article/47bda2ddaee24e27979c80f2bea5f4352022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S193652332100276Xhttps://doaj.org/toc/1936-5233α-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.Yoichi TakakusagiAya SugyoAtsushi B. TsujiHitomi SudoMasahiro YasunagaYasuhiro MatsumuraFumio SugawaraKengo SakaguchiTatsuya HigashiElsevierarticleRefractory cancerMolecular radiotherapyTherapeutic nuclear medicineRadionuclideNeoangiogenesisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101285- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Refractory cancer Molecular radiotherapy Therapeutic nuclear medicine Radionuclide Neoangiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Refractory cancer Molecular radiotherapy Therapeutic nuclear medicine Radionuclide Neoangiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yoichi Takakusagi Aya Sugyo Atsushi B. Tsuji Hitomi Sudo Masahiro Yasunaga Yasuhiro Matsumura Fumio Sugawara Kengo Sakaguchi Tatsuya Higashi The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
description	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.
format	article
author	Yoichi Takakusagi Aya Sugyo Atsushi B. Tsuji Hitomi Sudo Masahiro Yasunaga Yasuhiro Matsumura Fumio Sugawara Kengo Sakaguchi Tatsuya Higashi
author_facet	Yoichi Takakusagi Aya Sugyo Atsushi B. Tsuji Hitomi Sudo Masahiro Yasunaga Yasuhiro Matsumura Fumio Sugawara Kengo Sakaguchi Tatsuya Higashi
author_sort	Yoichi Takakusagi
title	The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
title_short	The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
title_full	The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
title_fullStr	The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
title_full_unstemmed	The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
title_sort	natural sulfoglycolipid derivative sqap improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model bxpc-3
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/47bda2ddaee24e27979c80f2bea5f435
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The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3

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