PMID- 25761504
OWN - NLM
STAT- MEDLINE
DCOM- 20151224
LR  - 20181202
IS  - 1361-6560 (Electronic)
IS  - 0031-9155 (Linking)
VI  - 60
IP  - 6
DP  - 2015 Mar 21
TI  - Exploring the quantitative relationship between metabolism and enzymatic 
      phenotype by physiological modeling of glucose metabolism and lactate oxidation 
      in solid tumors.
PG  - 2547-71
LID - 10.1088/0031-9155/60/6/2547 [doi]
AB  - Molecular imaging using PET or hyperpolarized MRI can characterize tumor 
      phenotypes by assessing the related metabolism of certain substrates. However, 
      the interpretation of the substrate turnover in terms of a pathophysiological 
      understanding is not straightforward and only semiquantitative. The metabolism of 
      imaging probes is influenced by a number of factors, such as the microvascular 
      structure or the expression of key enzymes. This study aims to use computational 
      simulation to investigate the relationship between the metabolism behind 
      molecular imaging and the underlying tumor phenotype. The study focused on the 
      pathways of glucose metabolism and lactate oxidation in order to establish the 
      quantitative relationship between the expression of several transporters (GLUT, 
      MCT1 and MCT4), expression of the enzyme hexokinase (HK), microvasculature and 
      the metabolism of glucose or lactate and the extracellular pH distribution. A 
      computational model for a 2D tumor tissue phantom was constructed and the 
      spatio-temporal evolution of related species (e.g. oxygen, glucose, lactate, 
      protons, bicarbonate ions) was estimated by solving reaction-diffusion equations. 
      The proposed model was tested by the verification of the simulation results using 
      in vivo and in vitro literature data. The influences of different expression 
      levels of GLUT, MCT1, MCT4, HK and microvessel distribution on substrate 
      concentrations were analyzed. The major results are consistent with experimental 
      data (e.g. GLUT is more influential to glycolytic flux than HK; extracellular pH 
      is not correlated with MCT expressions) and provide theoretical interpretation of 
      the co-influence of multiple factors of the tumor microenvironment. This 
      computational simulation may assist the generation of hypotheses to bridge the 
      discrepancy between tumor metabolism and the functions of transporters and 
      enzymes. It has the potential to accelerate the development of multi-modal 
      imaging strategies for assessment of tumor phenotypes.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitat 
      Munchen, Munich, Germany.
FAU - Vaupel, Peter
AU  - Vaupel P
FAU - Ziegler, Sibylle I
AU  - Ziegler SI
FAU - Shi, Kuangyu
AU  - Shi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150312
PL  - England
TA  - Phys Med Biol
JT  - Physics in medicine and biology
JID - 0401220
RN  - 0 (Glucose Transport Proteins, Facilitative)
RN  - 0 (Lactates)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Muscle Proteins)
RN  - 0 (SLC16A4 protein, human)
RN  - 0 (Symporters)
RN  - 0 (monocarboxylate transport protein 1)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *Computer Simulation
MH  - Glucose/*metabolism
MH  - Glucose Transport Proteins, Facilitative/metabolism
MH  - Hexokinase/metabolism
MH  - Humans
MH  - Lactates/*metabolism
MH  - Monocarboxylic Acid Transporters/metabolism
MH  - Muscle Proteins/metabolism
MH  - Neoplasms/enzymology/*metabolism
MH  - Oxidation-Reduction
MH  - Phantoms, Imaging
MH  - *Phenotype
MH  - Symporters/metabolism
EDAT- 2015/03/13 06:00
MHDA- 2015/12/25 06:00
CRDT- 2015/03/13 06:00
PHST- 2015/03/13 06:00 [entrez]
PHST- 2015/03/13 06:00 [pubmed]
PHST- 2015/12/25 06:00 [medline]
AID - 10.1088/0031-9155/60/6/2547 [doi]
PST - ppublish
SO  - Phys Med Biol. 2015 Mar 21;60(6):2547-71. doi: 10.1088/0031-9155/60/6/2547. Epub 
      2015 Mar 12.