PMID- 21159611
OWN - NLM
STAT- MEDLINE
DCOM- 20110328
LR  - 20240322
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 9
IP  - 12
DP  - 2010 Dec
TI  - Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C 
      magnetic resonance spectroscopy.
PG  - 3278-88
LID - 10.1158/1535-7163.MCT-10-0706 [doi]
AB  - Nuclear spin hyperpolarization can dramatically increase the sensitivity of the 
      (13)C magnetic resonance experiment, allowing dynamic measurements of the 
      metabolism of hyperpolarized (13)C-labeled substrates in vivo. Here, we report a 
      preclinical study of the response of lymphoma tumors to the vascular disrupting 
      agent (VDA), combretastatin-A4-phosphate (CA4P), as detected by measuring changes 
      in tumor metabolism of hyperpolarized [1-(13)C]pyruvate and 
      [1,4-(13)C(2)]fumarate. These measurements were compared with dynamic contrast 
      agent-enhanced magnetic resonance imaging (DCE-MRI) measurements of tumor 
      vascular function and diffusion-weighted MRI (DW-MRI) measurements of the tumor 
      cell necrosis that resulted from subsequent loss of tumor perfusion. The rate 
      constant describing flux of hyperpolarized (13)C label between [1-(13)C]pyruvate 
      and lactate was decreased by 34% within 6 hours of CA4P treatment and remained at 
      this lower level at 24 hours. The rate constant describing production of labeled 
      malate from hyperpolarized [1,4-(13)C(2)]fumarate increased 1.6-fold and 2.5-fold 
      at 6 and 24 hours after treatment, respectively, and correlated with the degree 
      of necrosis detected in histologic sections. Although DCE-MRI measurements showed 
      a substantial reduction in perfusion at 6 hours after treatment, which had 
      recovered by 24 hours, DW-MRI showed no change in the apparent diffusion 
      coefficient of tumor water at 6 hours after treatment, although there was a 32% 
      increase at 24 hours (P < 0.02) when regions of extensive necrosis were observed 
      by histology. Measurements of hyperpolarized [1-(13)C]pyruvate and 
      [1,4-(13)C(2)]fumarate metabolism may provide, therefore, a more sustained and 
      sensitive indicator of response to a VDA than DCE-MRI or DW-MRI, respectively.
CI  - (c)2010 AACR.
FAU - Bohndiek, Sarah E
AU  - Bohndiek SE
AD  - Department of Biochemistry, University of Cambridge, Cambridge, UK.
FAU - Kettunen, Mikko I
AU  - Kettunen MI
FAU - Hu, De-en
AU  - Hu DE
FAU - Witney, Timothy H
AU  - Witney TH
FAU - Kennedy, Brett W C
AU  - Kennedy BW
FAU - Gallagher, Ferdia A
AU  - Gallagher FA
FAU - Brindle, Kevin M
AU  - Brindle KM
LA  - eng
GR  - C197/A3514/Cancer Research UK/United Kingdom
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Carbon Isotopes)
RN  - 0 (Contrast Media)
RN  - 0 (Fumarates)
RN  - 0 (Stilbenes)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - I5590ES2QZ (fosbretabulin)
SB  - IM
MH  - Angiogenesis Inhibitors/chemistry/*therapeutic use
MH  - Animals
MH  - Carbon Isotopes
MH  - Contrast Media
MH  - Diffusion Magnetic Resonance Imaging
MH  - Fumarates/administration & dosage/pharmacology
MH  - Injections, Intravenous
MH  - Magnetic Resonance Spectroscopy/*methods
MH  - Mice
MH  - Neoplasms/*blood supply/*drug therapy/enzymology/pathology
MH  - Neovascularization, Pathologic/*drug therapy
MH  - Pyruvic Acid/administration & dosage/pharmacology
MH  - Stilbenes/chemistry/*therapeutic use
MH  - Time Factors
PMC - PMC3003424
MID - UKMS32221
OID - NLM: UKMS32221
EDAT- 2010/12/17 06:00
MHDA- 2011/03/29 06:00
PMCR- 2011/06/01
CRDT- 2010/12/17 06:00
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/03/29 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - 9/12/3278 [pii]
AID - 10.1158/1535-7163.MCT-10-0706 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2010 Dec;9(12):3278-88. doi: 10.1158/1535-7163.MCT-10-0706.