Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals

Takamatsu, Masayuki; Ueno, Jumpei; Toda, Taketo; Shimoyama, Atsushi; Mayusumi, Koki; Kabayama, Kazuya; Kadonaga, Yuichiro; Shirakami, Yoshifumi; Watabe, Tadashi; Yoshiya, Taku; Ooe, Kazuhiro; Murakami, Masashi; Toyoshima, Atsushi; Haba, Hiromitsu; Cardinale, Jens; Giesel, Frederik; Kaneda-Nakashima, Kazuko; Fukase, Koichi

doi:https://doi.org/10.1007/s10967-026-10999-6

Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals

Takamatsu, Masayuki; Ueno, Jumpei; Toda, Taketo et al.

Journal of Radioanalytical and Nuclear Chemistry, 2026

Number of Access:534（2026-09-16 22:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/106026

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
JRadioanalNuclChem_10999-6	pdf	None	899 KB	20	2026.08.06

Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals
Creator	NRID 1000001000322 1000001000322 ORCID 0009-0003-4810-065X 0009-0003-4810-065X researchmap permalink takamatsum takamatsum Scopus Author ID 56399097000 56399097000 CreatorName Takamatsu, Masayuki
	CreatorName Ueno, Jumpei
	CreatorName Toda, Taketo
	NRID 1000090625055 1000090625055 ORCID 0000-0003-1910-0450 0000-0003-1910-0450 researchmap permalink ashimo_ ashimo_ Scopus Author ID 18438446300 18438446300 CreatorName Shimoyama, Atsushi
	CreatorName Mayusumi, Koki
	NRID 1000000399974 1000000399974 ORCID 0000-0002-7583-5454 0000-0002-7583-5454 researchmap permalink KK007398 KK007398 Scopus Author ID 6602724377 6602724377 CreatorName Kabayama, Kazuya
	NRID 1000030836903 1000030836903 researchmap permalink 3456 3456 Scopus Author ID 25928507900 25928507900 CreatorName Kadonaga, Yuichiro
	NRID 1000000560400 1000000560400 ORCID 0000-0003-2352-9057 0000-0003-2352-9057 researchmap permalink e5221 e5221 Scopus Author ID 6603428576 6603428576 CreatorName Shirakami, Yoshifumi
	NRID 1000090648932 1000090648932 ORCID 0000-0001-8658-2395 0000-0001-8658-2395 researchmap permalink twosaka2018 twosaka2018 Scopus Author ID 57421862900 57421862900 CreatorName Watabe, Tadashi
	CreatorName Yoshiya, Taku
	NRID 1000090610303 1000090610303 researchmap permalink 046214597 046214597 Scopus Author ID 16070507900 16070507900 CreatorName Ooe, Kazuhiro
	ORCID 0000-0001-7936-2263 0000-0001-7936-2263 researchmap permalink murakami-masashi murakami-masashi Scopus Author ID 55378274900 55378274900 NRID 1000081011517 1000081011517 CreatorName Murakami, Masashi
	NRID 1000040414578 1000040414578 researchmap permalink read0076538 read0076538 Scopus Author ID 15833301700 15833301700 CreatorName Toyoshima, Atsushi
	NRID 1000060360624 1000060360624 CreatorName Haba, Hiromitsu
	CreatorName Cardinale, Jens
	CreatorName Giesel, Frederik
	NRID 1000000533209 1000000533209 ORCID 0000-0001-6657-5059 0000-0001-6657-5059 researchmap permalink read0131912 read0131912 CreatorName Kaneda-Nakashima, Kazuko
	NRID 1000080192722 1000080192722 ORCID 0000-0001-8844-0710 0000-0001-8844-0710 researchmap permalink read0076573 read0076573 Scopus Author ID 7005633724 7005633724 CreatorName Fukase, Koichi
Subject	Astatine-211
	Cytotoxic effect
	Fibroblast activation protein (FAP)
	Radiopharmaceutical
	α-emitter
Description	Takamatsu M., Ueno J., Toda T., et al. Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals. Journal of Radioanalytical and Nuclear Chemistry , (2026); https://doi.org/10.1007/s10967-026-10999-6.
Description	The version of record of this article, first published in Journal of Radioanalytical and Nuclear Chemistry, is available online at Publisher’s website: https://doi.org/10.1007/s10967-026-10999-6
Abstract	Fibroblast activation protein (FAP), which is overexpressed in cancer-associated fibroblasts (CAFs) is an attractive stromal target for a-therapy. We previously reported moderate anti-tumor effects of ²¹¹At-labeled FAP inhibitors (FAPI) in a PANC-1 xenograft mouse model, where insufficient tumor accumulation and the absence of FAP expression in tumor cells limited therapeutic efficacy. In this study, we performed in vitro mechanistic follow-up experiments using FAP-negative PANC-1 cells to clarify the radioactivity–time-dependent cytotoxicity of ²¹¹At-labeled FAPI compared with free ²¹¹At (non-conjugated ²¹¹At). We found that, whereas free ²¹¹At showed only limited cytotoxicity, ²¹¹At-labeled FAPI exerted significant cytotoxic effects. Systematic variation of activity concentrations and exposure durations revealed that cytotoxicity depended primarily on sustained pericellular exposure rather than initial radioactivity levels. These findings provide mechanistic, hypothesis-generating insight into how CAF-targeted ²¹¹At radiopharmaceuticals can exert effective cytotoxicity without direct tumor cell targeting and may inform future optimization of stromal-targeted a-therapy, while further in vivo and translational studies will be required.
Publisher	Springer Nature
Source Title	Journal of Radioanalytical and Nuclear Chemistry
Date of Issued	2026-06-30
Language	English
Handle URL	https://hdl.handle.net/11094/106026
PISSN	02365731
eISSN	15882780
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s10967-026-10999-6
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Radioanalytical and Nuclear Chemistry. 2026
DC.title	Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals
DC.creator	Takamatsu, Masayuki
	Ueno, Jumpei
	Toda, Taketo
	Shimoyama, Atsushi
	Mayusumi, Koki
	Kabayama, Kazuya
	Kadonaga, Yuichiro
	Shirakami, Yoshifumi
	Watabe, Tadashi
	Yoshiya, Taku
	Ooe, Kazuhiro
	Murakami, Masashi
	Toyoshima, Atsushi
	Haba, Hiromitsu
	Cardinale, Jens
	Giesel, Frederik
	Kaneda-Nakashima, Kazuko
	Fukase, Koichi
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-06-30
DC.identifier	https://doi.org/10.1007/s10967-026-10999-6
DC.subject	Astatine-211
	Cytotoxic effect
	Fibroblast activation protein (FAP)
	Radiopharmaceutical
	α-emitter
DC.description	Takamatsu M., Ueno J., Toda T., et al. Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals. Journal of Radioanalytical and Nuclear Chemistry , (2026); https://doi.org/10.1007/s10967-026-10999-6.
DC.description	The version of record of this article, first published in Journal of Radioanalytical and Nuclear Chemistry, is available online at Publisher’s website: https://doi.org/10.1007/s10967-026-10999-6
DCTERMS.abstract	Fibroblast activation protein (FAP), which is overexpressed in cancer-associated fibroblasts (CAFs) is an attractive stromal target for a-therapy. We previously reported moderate anti-tumor effects of ²¹¹At-labeled FAP inhibitors (FAPI) in a PANC-1 xenograft mouse model, where insufficient tumor accumulation and the absence of FAP expression in tumor cells limited therapeutic efficacy. In this study, we performed in vitro mechanistic follow-up experiments using FAP-negative PANC-1 cells to clarify the radioactivity–time-dependent cytotoxicity of ²¹¹At-labeled FAPI compared with free ²¹¹At (non-conjugated ²¹¹At). We found that, whereas free ²¹¹At showed only limited cytotoxicity, ²¹¹At-labeled FAPI exerted significant cytotoxic effects. Systematic variation of activity concentrations and exposure durations revealed that cytotoxicity depended primarily on sustained pericellular exposure rather than initial radioactivity levels. These findings provide mechanistic, hypothesis-generating insight into how CAF-targeted ²¹¹At radiopharmaceuticals can exert effective cytotoxicity without direct tumor cell targeting and may inform future optimization of stromal-targeted a-therapy, while further in vivo and translational studies will be required.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	106026
citation_title	Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals
citation_author	Takamatsu, Masayuki
	Ueno, Jumpei
	Toda, Taketo
	Shimoyama, Atsushi
	Mayusumi, Koki
	Kabayama, Kazuya
	Kadonaga, Yuichiro
	Shirakami, Yoshifumi
	Watabe, Tadashi
	Yoshiya, Taku
	Ooe, Kazuhiro
	Murakami, Masashi
	Toyoshima, Atsushi
	Haba, Hiromitsu
	Cardinale, Jens
	Giesel, Frederik
	Kaneda-Nakashima, Kazuko
	Fukase, Koichi
citation_publisher	Springer Nature
citation_language	English
citation_date	2026-06-30
citation_journal_title	Journal of Radioanalytical and Nuclear Chemistry
citation_doi	https://doi.org/10.1007/s10967-026-10999-6
citation_public_url	https://hdl.handle.net/11094/106026

Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals

Link to primary information

Item Information

Show details