MRI with magnetic nanoparticles monitors downstream anti-angiogenic effects of mTOR inhibition

Alexander Guimaraes, Robert Ross, Jose L. Figuereido, Peter Waterman, Ralph Weissleder

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 ∼750 μl, 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 ΔR2 (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 fromcontrol (p

Original languageEnglish (US)
Pages (from-to)314-320
Number of pages7
JournalMolecular Imaging and Biology
Volume13
Issue number2
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Sirolimus
Nanoparticles
Blood Vessels
Magnetic Resonance Imaging
Nude Mice
Vascular Endothelial Growth Factor A
Linear Models
Histology
Clinical Trials
Muscles
Therapeutics
Neoplasms

Keywords

  • Angiogenesis
  • Magnetic nanoparticle imaging
  • Magnetic resonance imaging
  • MRI
  • mTOR
  • Renal cell cancer
  • Ultrasmall superparamagnetic iron oxide nanoparticle

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

MRI with magnetic nanoparticles monitors downstream anti-angiogenic effects of mTOR inhibition. / Guimaraes, Alexander; Ross, Robert; Figuereido, Jose L.; Waterman, Peter; Weissleder, Ralph.

In: Molecular Imaging and Biology, Vol. 13, No. 2, 04.2011, p. 314-320.

Research output: Contribution to journalArticle

Guimaraes, Alexander ; Ross, Robert ; Figuereido, Jose L. ; Waterman, Peter ; Weissleder, Ralph. / MRI with magnetic nanoparticles monitors downstream anti-angiogenic effects of mTOR inhibition. In: Molecular Imaging and Biology. 2011 ; Vol. 13, No. 2. pp. 314-320.
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