Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

Aoki, Masanao; Watabe, Tadashi; Nagamori, Shushi; Naka, Sadahiro; Ikeda, Hayato; Kongpracha, Pornparn; Horitsugi, Genki; Kanai, Yasukazu; Shimosegawa, Eku; Kanai, Yoshikatsu; Hatazawa, Jun

doi:https://doi.org/10.1007/s12149-019-01346-9

Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

Aoki, Masanao; Watabe, Tadashi; Nagamori, Shushi et al.

Annals of Nuclear Medicine, 2019, 33(6), 394-403

Number of Access:31（2026-07-28 07:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/105195

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Title	Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2
Creator	CreatorName Aoki, Masanao
	NRID 1000090648932 1000090648932 ORCID 0000-0001-8658-2395 0000-0001-8658-2395 researchmap permalink twosaka2018 twosaka2018 Scopus Author ID 57421862900 57421862900 CreatorName Watabe, Tadashi
	NRID 1000090467572 1000090467572 CreatorName Nagamori, Shushi
	NRID 1000060599843 1000060599843 researchmap permalink _sada_ _sada_ CreatorName Naka, Sadahiro
	NRID 1000030649083 1000030649083 CreatorName Ikeda, Hayato
	NRID 1000070817767 1000070817767 CreatorName Kongpracha, Pornparn
	NRID 1000070646231 1000070646231 CreatorName Horitsugi, Genki
	NRID 1000060397643 1000060397643 ORCID 0009-0004-3069-2789 0009-0004-3069-2789 researchmap permalink yaskanai yaskanai Scopus Author ID 55575124400 55575124400 CreatorName Kanai, Yasukazu
	NRID 1000030370258 1000030370258 CreatorName Shimosegawa, Eku
	NRID 1000060204533 1000060204533 researchmap permalink read0063550 read0063550 Scopus Author ID 55575124400 55575124400 CreatorName Kanai, Yoshikatsu
	NRID 1000070198745 1000070198745 CreatorName Hatazawa, Jun
Subject	C6 glioma
	LAT1
	MIA PaCa-2
	Small-animal PET
	Tumoral blood flow
Description	Aoki M., Watabe T., Nagamori S., et al. Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2. Annals of Nuclear Medicine 33, 394–403 (2019).
Description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12149-019-01346-9
Abstract	Objective: L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-FBPA) and L-3-¹⁸F-alpha-methyl tyrosine (¹⁸F-FAMT), in relation to the tumor blood flow, using rat xenograft models. Methods: Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of ¹⁸F-FAMT or ¹⁸F-FBPA (scan duration = 70 min) following ¹⁵O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K₁, k₂, and total distribution volume (Vₜ) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vₜ. Tumor blood flow (TBF) was represented by the K₁ value in ¹⁵O-water PET. Results: LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vₜ values of both ¹⁸F-FBPA and ¹⁸F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vₜ value of either ¹⁸F-FBPA or ¹⁸F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. Conclusions: This study revealed that total distribution volumes of the LAT1-targeting PET tracers ¹⁸F-FBPA and ¹⁸F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.
Publisher	Springer Tokyoorders
Source Title	Annals of Nuclear Medicine
Volume (Issue)	33(6)
Page	394-403
Date of Issued	2019-02-28
Language	English
Handle URL	https://hdl.handle.net/11094/105195
PISSN	09147187
eISSN	18646433
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1007/s12149-019-01346-9
Access Rights	open access
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Annals of Nuclear Medicine. 2019, 33(6), p. 394-403
DC.title	Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2
DC.creator	Aoki, Masanao
	Watabe, Tadashi
	Nagamori, Shushi
	Naka, Sadahiro
	Ikeda, Hayato
	Kongpracha, Pornparn
	Horitsugi, Genki
	Kanai, Yasukazu
	Shimosegawa, Eku
	Kanai, Yoshikatsu
	Hatazawa, Jun
DC.publisher	Springer Tokyoorders
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-02-28
DC.identifier	https://doi.org/10.1007/s12149-019-01346-9
DC.subject	C6 glioma
	LAT1
	MIA PaCa-2
	Small-animal PET
	Tumoral blood flow
DC.description	Aoki M., Watabe T., Nagamori S., et al. Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2. Annals of Nuclear Medicine 33, 394–403 (2019).
DC.description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12149-019-01346-9
DCTERMS.abstract	Objective: L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-FBPA) and L-3-¹⁸F-alpha-methyl tyrosine (¹⁸F-FAMT), in relation to the tumor blood flow, using rat xenograft models. Methods: Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of ¹⁸F-FAMT or ¹⁸F-FBPA (scan duration = 70 min) following ¹⁵O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K₁, k₂, and total distribution volume (Vₜ) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vₜ. Tumor blood flow (TBF) was represented by the K₁ value in ¹⁵O-water PET. Results: LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vₜ values of both ¹⁸F-FBPA and ¹⁸F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vₜ value of either ¹⁸F-FBPA or ¹⁸F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. Conclusions: This study revealed that total distribution volumes of the LAT1-targeting PET tracers ¹⁸F-FBPA and ¹⁸F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.
DC.format	105195
citation_title	Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2
citation_author	Aoki, Masanao
	Watabe, Tadashi
	Nagamori, Shushi
	Naka, Sadahiro
	Ikeda, Hayato
	Kongpracha, Pornparn
	Horitsugi, Genki
	Kanai, Yasukazu
	Shimosegawa, Eku
	Kanai, Yoshikatsu
	Hatazawa, Jun
citation_publisher	Springer Tokyoorders
citation_language	English
citation_date	2019-02-28
citation_journal_title	Annals of Nuclear Medicine
citation_volume	33
citation_issue	6
citation_firstpage	394
citation_lastpage	403
citation_doi	https://doi.org/10.1007/s12149-019-01346-9
citation_public_url	https://hdl.handle.net/11094/105195

Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

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