Related Experiment Video
Updated: Jun 12, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
MRI with magnetic nanoparticles monitors downstream anti-angiogenic effects of mTOR inhibition
Alexander R Guimaraes1, Robert Ross, Jose L Figuereido
1Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA. aguimaraes1@partners.org
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 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.
Insights
Magnetic resonance imaging (MRI) noninvasively monitored anti-angiogenic effects of mammalian target of rapamycin (mTOR) inhibition in tumors. This technique accurately assessed changes in vascular volume fraction, correlating with tumor microvascular density.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Angiogenesis is crucial for tumor growth and a target for cancer therapies.
- Mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors are key anti-angiogenic treatments.
- Noninvasive monitoring of anti-angiogenic treatment efficacy is essential for optimizing cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of magnetic resonance imaging (MRI) in monitoring the anti-angiogenic effects of mammalian target of rapamycin (mTOR) inhibition.
- To assess the correlation between MRI-derived vascular volume fraction (VVF) and histological microvascular density (MVD).
- To compare the anti-angiogenic effects of an mTOR inhibitor with a VEGF inhibitor using MRI.
Main Methods:
- Subcutaneous renal cell carcinoma xenografts were established in nude mice.
- Tumor-bearing mice were treated with rapamycin (mTOR inhibitor), sorafenib (VEGF inhibitor), or saline control for 4 weeks.
- Weekly MRI was performed using magnetic iron oxide nanoparticles (MNP) to quantify VVF, which was then compared to MVD via histology.
Main Results:
- A strong correlation was observed between MRI-derived VVF and histological MVD (R² = 0.95).
- All treatment groups showed a significant reduction in VVF compared to the control group (p < 0.05).
- The anti-angiogenic effect of rapamycin was comparable to high-dose sorafenib, as assessed by VVF changes.
Conclusions:
- MRI with MNP provides a noninvasive method for in vivo monitoring of anti-angiogenic therapy targeting mTOR.
- This imaging technique can accurately quantify treatment-induced changes in tumor vascularity.
- MRI-based monitoring holds promise for guiding and optimizing anti-angiogenic cancer treatments.
