PMID- 20559742
OWN - NLM
STAT- MEDLINE
DCOM- 20110620
LR  - 20211203
IS  - 1860-2002 (Electronic)
IS  - 1536-1632 (Linking)
VI  - 13
IP  - 2
DP  - 2011 Apr
TI  - MRI with magnetic nanoparticles monitors downstream anti-angiogenic effects of 
      mTOR inhibition.
PG  - 314-20
LID - 10.1007/s11307-010-0357-2 [doi]
AB  - PURPOSE: To study the effect of mammalian target of rapamycin (mTOR) inhibition 
      on angiogenesis with magnetic resonance imaging (MRI) using magnetic iron oxide 
      nanoparticles (MNP). PROCEDURES: One million CAK-1 renal cell carcinoma cells 
      were subcutaneously implanted into each of 20 nude mice. When tumors reached  approximately 750 
      mul, four daily treatment arms began and continued for 4 weeks: rapamycin (mTOR 
      inhibitor) 10 mg/kg/day; sorafenib (VEGF inhibitor) high dose (80 mg/kg/day) and 
      low dose (30 mg/kg/day); and saline control. Weekly MRI (4.7 T Bruker Pharmascan) 
      was performed before and after IV MION-48, a prototype MNP similar to MNP in 
      clinical trials. Vascular volume fraction (VVF) was quantified as DeltaR2 (from 
      multi-contrast T2 sequences) and normalized to assumed muscle VVF of 3%. Linear 
      regression compared VVF to microvascular density (MVD) as determined by 
      histology. RESULTS: VVF correlated with MVD (R(2) = 0.95). VVF in all treatment 
      arms differed from control (p < 0.05) and declined weekly with treatment. VVF 
      changes with rapamycin were similar to high-dose sorafenib. CONCLUSION: This 
      study demonstrates noninvasive, in vivo anti-angiogenic monitoring using MRI of 
      mTOR inhibition.
FAU - Guimaraes, Alexander R
AU  - Guimaraes AR
AD  - Center for Molecular Imaging Research, Department of Radiology, Massachusetts 
      General Hospital, Charlestown, MA, USA. aguimaraes1@partners.org
FAU - Ross, Robert
AU  - Ross R
FAU - Figuereido, Jose L
AU  - Figuereido JL
FAU - Waterman, Peter
AU  - Waterman P
FAU - Weissleder, Ralph
AU  - Weissleder R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Imaging Biol
JT  - Molecular imaging and biology
JID - 101125610
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (monocrystalline iron oxide nanoparticle)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - XM0M87F357 (Ferrosoferric Oxide)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Ferrosoferric Oxide
MH  - Magnetic Resonance Imaging/*methods
MH  - Mice
MH  - Mice, Nude
MH  - Microvessels/drug effects/pathology
MH  - Nanoparticles
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Transplantation, Heterologous
EDAT- 2010/06/19 06:00
MHDA- 2011/06/21 06:00
CRDT- 2010/06/19 06:00
PHST- 2010/06/19 06:00 [entrez]
PHST- 2010/06/19 06:00 [pubmed]
PHST- 2011/06/21 06:00 [medline]
AID - 10.1007/s11307-010-0357-2 [doi]
PST - ppublish
SO  - Mol Imaging Biol. 2011 Apr;13(2):314-20. doi: 10.1007/s11307-010-0357-2.