ArticleJournal of controlled release : official journal of the Controlled Release Society2013
Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
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- Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.Neuro-oncology · 2024Article
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- Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting.Science China. Life sciences · 2022Article
- Breaking barriers: Neurodegenerative repercussions of radiotherapy induced damage on the blood-brain and blood-tumor barrier.Free radical biology & medicine · 2022Review
- The blood-tumour barrier in cancer biology and therapy.Nature reviews. Clinical oncology · 2021Review
- Drug Repurposing in Medulloblastoma: Challenges and Recommendations.Current treatment options in oncology · 2020Review
- Genes that Mediate Metastasis across the Blood-Brain Barrier.Trends in cancer · 2020Review
- Trifluoperazine prolongs the survival of experimental brain metastases by STAT3-dependent lysosomal membrane permeabilization.American journal of cancer research · 2020Article
- Immune-mediated ECM depletion improves tumour perfusion and payload delivery.EMBO molecular medicine · 2019Article
- Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis.Acta neuropathologica communications · 2019Article
- Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.Nature communications · 2018Article
- Multimodal Molecular Imaging: Current Status and Future Directions.Contrast media & molecular imaging · 2018Review
- Article
- Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer.European radiology · 2017Observational
- Pathological Brain Detection Using Weiner Filtering, 2D-Discrete Wavelet Transform, Probabilistic PCA, and Random Subspace Ensemble Classifier.Computational intelligence and neuroscience · 2017Article
- Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment.Translational oncology · 2016Article
- A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines.International journal of molecular sciences · 2015Article
- Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy.Translational oncology · 2015Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.
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Registered trials
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