Colorectal tumor cells treated with 5FU, oxaliplatin, irinotecan and cetuximab exhibit changes in 18F-FDG incorporation corresponding with hexokinase activity and glucose transport

Rituka I. Sharma, Tim A. D. Smith

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The purpose of this study was to determine therapy-induced changes in F-18-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in F-18-FDG incorporation. Methods: SW620 cells were treated with inhibitory concentration of 50% (IC50) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. F-18-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells. Results: Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. F-18-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased F-18-FDG incorporation. Decreased F-18-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased F-18-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment. Conclusion: F-18-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC50 doses of cetuximab also exhibit decreased F-18-FDG.

Original languageEnglish
Pages (from-to)1386-1394
Number of pages8
JournalJournal of Nuclear Medicine
Volume49
Issue number8
Early online date16 Jul 2008
DOIs
Publication statusPublished - Aug 2008

Keywords

  • oncology
  • PET
  • cetuximab
  • colorectal
  • F-18-FDG
  • glucose transport
  • positron-emission-tomography
  • colon-cancer cells
  • in-vitro
  • liver metastases
  • lung-cancer
  • chemotherapy
  • expression
  • EGFR
  • 5-fluorouracil

Cite this

@article{76fc543e61014df9ab272812e7cc4634,
title = "Colorectal tumor cells treated with 5FU, oxaliplatin, irinotecan and cetuximab exhibit changes in 18F-FDG incorporation corresponding with hexokinase activity and glucose transport",
abstract = "The purpose of this study was to determine therapy-induced changes in F-18-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in F-18-FDG incorporation. Methods: SW620 cells were treated with inhibitory concentration of 50{\%} (IC50) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. F-18-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells. Results: Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. F-18-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased F-18-FDG incorporation. Decreased F-18-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased F-18-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment. Conclusion: F-18-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC50 doses of cetuximab also exhibit decreased F-18-FDG.",
keywords = "oncology, PET, cetuximab, colorectal, F-18-FDG, glucose transport, positron-emission-tomography, colon-cancer cells, in-vitro, liver metastases, lung-cancer, chemotherapy, expression, EGFR, 5-fluorouracil",
author = "Sharma, {Rituka I.} and Smith, {Tim A. D.}",
year = "2008",
month = "8",
doi = "10.2967/jnumed.107.047886",
language = "English",
volume = "49",
pages = "1386--1394",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "8",

}

TY - JOUR

T1 - Colorectal tumor cells treated with 5FU, oxaliplatin, irinotecan and cetuximab exhibit changes in 18F-FDG incorporation corresponding with hexokinase activity and glucose transport

AU - Sharma, Rituka I.

AU - Smith, Tim A. D.

PY - 2008/8

Y1 - 2008/8

N2 - The purpose of this study was to determine therapy-induced changes in F-18-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in F-18-FDG incorporation. Methods: SW620 cells were treated with inhibitory concentration of 50% (IC50) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. F-18-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells. Results: Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. F-18-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased F-18-FDG incorporation. Decreased F-18-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased F-18-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment. Conclusion: F-18-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC50 doses of cetuximab also exhibit decreased F-18-FDG.

AB - The purpose of this study was to determine therapy-induced changes in F-18-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in F-18-FDG incorporation. Methods: SW620 cells were treated with inhibitory concentration of 50% (IC50) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. F-18-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells. Results: Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. F-18-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased F-18-FDG incorporation. Decreased F-18-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased F-18-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment. Conclusion: F-18-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC50 doses of cetuximab also exhibit decreased F-18-FDG.

KW - oncology

KW - PET

KW - cetuximab

KW - colorectal

KW - F-18-FDG

KW - glucose transport

KW - positron-emission-tomography

KW - colon-cancer cells

KW - in-vitro

KW - liver metastases

KW - lung-cancer

KW - chemotherapy

KW - expression

KW - EGFR

KW - 5-fluorouracil

U2 - 10.2967/jnumed.107.047886

DO - 10.2967/jnumed.107.047886

M3 - Article

VL - 49

SP - 1386

EP - 1394

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 8

ER -