Levels of human equilibrative nucleoside transporter-1 are higher in proliferating regions of A549 tumor cells grown as tumor xenografts in vivo

David A. Plotnik, Camille Asher, Stephanie K. Chu, Robert S. Miyaoka, Gregory G. Garwin, Brian W. Johnson, Tiffany Li, Kenneth Krohn, Jeffrey L. Schwartz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission tomography (PET)-based identification of tumor chemosensitivity that is mediated by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates transport of FLT into cells and elevated levels of FLT are associated with both larger FLT-PET signals and increased response to nucleoside-based chemotherapies. FLT-PET is also used as a measure of tumor proliferation. The present study examined the extent to which ENT1 levels vary in a proliferation-dependent manner in tumor cells in vivo. Methods: The human adenocarcinoma cell line A549 was used to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using PET, and further examined ex vivo using autoradiography. FLT uptake patterns were compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation markers Ki67 and BrdU. Results: Regional differences in FLT uptake matched differences in IHC proliferation markers. All cells stained for ENT1, but the staining intensity was twice as high for Ki67+ cells than for Ki67- cells. Conclusions: Under in vivo conditions, proliferating regions of tumors show increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.

Original languageEnglish (US)
Pages (from-to)1161-1166
Number of pages6
JournalNuclear Medicine and Biology
Volume39
Issue number8
DOIs
StatePublished - Nov 2012
Externally publishedYes

Fingerprint

Equilibrative Nucleoside Transporter 1
Heterografts
Positron-Emission Tomography
Neoplasms
Bromodeoxyuridine
Autoradiography
Nucleosides
Nude Mice
human SLC29A1 protein
A549 Cells
Adenocarcinoma
Staining and Labeling
Drug Therapy

Keywords

  • ENT1
  • FLT-PET Imaging
  • Ki67
  • Tumor Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Levels of human equilibrative nucleoside transporter-1 are higher in proliferating regions of A549 tumor cells grown as tumor xenografts in vivo. / Plotnik, David A.; Asher, Camille; Chu, Stephanie K.; Miyaoka, Robert S.; Garwin, Gregory G.; Johnson, Brian W.; Li, Tiffany; Krohn, Kenneth; Schwartz, Jeffrey L.

In: Nuclear Medicine and Biology, Vol. 39, No. 8, 11.2012, p. 1161-1166.

Research output: Contribution to journalArticle

Plotnik, David A. ; Asher, Camille ; Chu, Stephanie K. ; Miyaoka, Robert S. ; Garwin, Gregory G. ; Johnson, Brian W. ; Li, Tiffany ; Krohn, Kenneth ; Schwartz, Jeffrey L. / Levels of human equilibrative nucleoside transporter-1 are higher in proliferating regions of A549 tumor cells grown as tumor xenografts in vivo. In: Nuclear Medicine and Biology. 2012 ; Vol. 39, No. 8. pp. 1161-1166.
@article{b54e72bf7ec348fd96563fff5853075e,
title = "Levels of human equilibrative nucleoside transporter-1 are higher in proliferating regions of A549 tumor cells grown as tumor xenografts in vivo",
abstract = "3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission tomography (PET)-based identification of tumor chemosensitivity that is mediated by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates transport of FLT into cells and elevated levels of FLT are associated with both larger FLT-PET signals and increased response to nucleoside-based chemotherapies. FLT-PET is also used as a measure of tumor proliferation. The present study examined the extent to which ENT1 levels vary in a proliferation-dependent manner in tumor cells in vivo. Methods: The human adenocarcinoma cell line A549 was used to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using PET, and further examined ex vivo using autoradiography. FLT uptake patterns were compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation markers Ki67 and BrdU. Results: Regional differences in FLT uptake matched differences in IHC proliferation markers. All cells stained for ENT1, but the staining intensity was twice as high for Ki67+ cells than for Ki67- cells. Conclusions: Under in vivo conditions, proliferating regions of tumors show increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.",
keywords = "ENT1, FLT-PET Imaging, Ki67, Tumor Cell Proliferation",
author = "Plotnik, {David A.} and Camille Asher and Chu, {Stephanie K.} and Miyaoka, {Robert S.} and Garwin, {Gregory G.} and Johnson, {Brian W.} and Tiffany Li and Kenneth Krohn and Schwartz, {Jeffrey L.}",
year = "2012",
month = "11",
doi = "10.1016/j.nucmedbio.2012.07.007",
language = "English (US)",
volume = "39",
pages = "1161--1166",
journal = "International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - Levels of human equilibrative nucleoside transporter-1 are higher in proliferating regions of A549 tumor cells grown as tumor xenografts in vivo

AU - Plotnik, David A.

AU - Asher, Camille

AU - Chu, Stephanie K.

AU - Miyaoka, Robert S.

AU - Garwin, Gregory G.

AU - Johnson, Brian W.

AU - Li, Tiffany

AU - Krohn, Kenneth

AU - Schwartz, Jeffrey L.

PY - 2012/11

Y1 - 2012/11

N2 - 3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission tomography (PET)-based identification of tumor chemosensitivity that is mediated by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates transport of FLT into cells and elevated levels of FLT are associated with both larger FLT-PET signals and increased response to nucleoside-based chemotherapies. FLT-PET is also used as a measure of tumor proliferation. The present study examined the extent to which ENT1 levels vary in a proliferation-dependent manner in tumor cells in vivo. Methods: The human adenocarcinoma cell line A549 was used to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using PET, and further examined ex vivo using autoradiography. FLT uptake patterns were compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation markers Ki67 and BrdU. Results: Regional differences in FLT uptake matched differences in IHC proliferation markers. All cells stained for ENT1, but the staining intensity was twice as high for Ki67+ cells than for Ki67- cells. Conclusions: Under in vivo conditions, proliferating regions of tumors show increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.

AB - 3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission tomography (PET)-based identification of tumor chemosensitivity that is mediated by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates transport of FLT into cells and elevated levels of FLT are associated with both larger FLT-PET signals and increased response to nucleoside-based chemotherapies. FLT-PET is also used as a measure of tumor proliferation. The present study examined the extent to which ENT1 levels vary in a proliferation-dependent manner in tumor cells in vivo. Methods: The human adenocarcinoma cell line A549 was used to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using PET, and further examined ex vivo using autoradiography. FLT uptake patterns were compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation markers Ki67 and BrdU. Results: Regional differences in FLT uptake matched differences in IHC proliferation markers. All cells stained for ENT1, but the staining intensity was twice as high for Ki67+ cells than for Ki67- cells. Conclusions: Under in vivo conditions, proliferating regions of tumors show increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.

KW - ENT1

KW - FLT-PET Imaging

KW - Ki67

KW - Tumor Cell Proliferation

UR - http://www.scopus.com/inward/record.url?scp=84867841072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867841072&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2012.07.007

DO - 10.1016/j.nucmedbio.2012.07.007

M3 - Article

C2 - 22985987

AN - SCOPUS:84867841072

VL - 39

SP - 1161

EP - 1166

JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology

JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology

SN - 0969-8051

IS - 8

ER -