PMID- 21492782
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20220129
IS  - 1872-9614 (Electronic)
IS  - 0969-8051 (Linking)
VI  - 38
IP  - 3
DP  - 2011 Apr
TI  - Changes in 2-fluoro-2-deoxy-D-glucose incorporation, hexokinase activity and 
      lactate production by breast cancer cells responding to treatment with the 
      anti-HER-2 antibody trastuzumab.
PG  - 339-46
LID - 10.1016/j.nucmedbio.2010.09.005 [doi]
AB  - INTRODUCTION: Changes in 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) incorporation 
      by tumors, detected using positron emission tomography, during response to 
      chemotherapy are utilized clinically in patient management. Here, the effect of 
      treatment with growth-inhibitory doses of the anti-human epidermal growth factor 
      receptor-2 antibody trastuzumab (Herceptin) on the incorporation of FDG by breast 
      tumor cells was measured along with hexokinase (HK) and glucose transport to 
      determine the potential of FDG-positron emission tomography in predicting 
      response to these biological anti-cancer therapies and their modulatory effects 
      on the steps involved in FDG incorporation. METHODS: The sensitivity to 
      trastuzumab of three breast tumor cell lines, SKBr3, MDA-MB-453 and MDA-MB-468, 
      expressing human epidermal growth factor receptor-2 at high, medium and low 
      levels, respectively, was determined using MTT 
      [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay over a 6-day 
      period, and a clonogenic assay was carried out after 7- and 10-day exposures. FDG 
      incorporation by cells treated with growth-inhibitory doses of trastuzumab was 
      carried out after 4 h and 2, 4 and 6 days of treatment. Glucose transport (rate 
      of uptake of the non-metabolizable analogue [(3)H]O-methyl-D-glucose), HK 
      activity and lactate production were measured on cells treated with inhibitory 
      doses of trastuzumab for 6 days. RESULTS: The IC(50) doses for SKBr3 and 
      MDA-MB-453 and the IC(20) dose for MDA-MB-468 after 6 days of treatment with 
      trastuzumab were 0.25, 1 and 170 mug/ml, respectively. FDG incorporation by SKBr3 
      and MDA-MB-453 cells was found to be decreased using IC(50) doses of trastuzumab 
      for 6 days. At the IC(50) doses, FDG incorporation was also decreased at 4 days 
      and, in the case of MDA-MB-453, even after 4 h of treatment. Decreased FDG 
      incorporation corresponded with decreased HK activity in these cells. Lactate 
      production, previously suggested to be a potential measure of response, was found 
      to be significantly decreased by SKBr3 and MDA-MB-453 cells responding to 
      trastuzumab. CONCLUSION: FDG incorporation at the tumor cell level is modulated 
      by treatment with growth-inhibitory doses of trastuzumab due to modulation of HK 
      activity. Changes in lactate production may also be a useful determinant of 
      response to trastuzumab.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Cheyne, Richard W
AU  - Cheyne RW
AD  - School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 
      2ZD, UK.
FAU - Trembleau, Laurent
AU  - Trembleau L
FAU - McLaughlin, Abbie
AU  - McLaughlin A
FAU - Smith, Tim A D
AU  - Smith TA
LA  - eng
GR  - 2006NOVPHD16/BCN_/Breast Cancer Now/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101203
PL  - United States
TA  - Nucl Med Biol
JT  - Nuclear medicine and biology
JID - 9304420
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EUY85H477I (thiazolyl blue)
RN  - IY9XDZ35W2 (Glucose)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*immunology/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Biological Transport/drug effects
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Fluorodeoxyglucose F18/*metabolism
MH  - Glucose/metabolism
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Lactic Acid/*biosynthesis
MH  - Receptor, ErbB-2/*immunology
MH  - Tetrazolium Salts/metabolism
MH  - Thiazoles/metabolism
MH  - Trastuzumab
MH  - Tumor Stem Cell Assay
EDAT- 2011/04/16 06:00
MHDA- 2011/08/24 06:00
CRDT- 2011/04/16 06:00
PHST- 2010/07/13 00:00 [received]
PHST- 2010/08/20 00:00 [revised]
PHST- 2010/09/08 00:00 [accepted]
PHST- 2011/04/16 06:00 [entrez]
PHST- 2011/04/16 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
AID - S0969-8051(10)00445-2 [pii]
AID - 10.1016/j.nucmedbio.2010.09.005 [doi]
PST - ppublish
SO  - Nucl Med Biol. 2011 Apr;38(3):339-46. doi: 10.1016/j.nucmedbio.2010.09.005. Epub 
      2010 Dec 3.