Journal
THERANOSTICS
Volume 6, Issue 8, Pages 1075-1084Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.13842
Keywords
SERRS molecular imaging; Raman spectroscopy; Image-guided surgery; Neurosurgery; Brain tumor treatment
Categories
Funding
- NIH [R01 EB017748, K08 CA16396]
- Damon Runyon Cancer Research Foundation [DRR-29-14]
- Pershing Square Sohn Cancer Research Alliance
- Dana Foundation Brain and Immuno-Imaging Grant
- Dana Neuroscience Scholar Award
- MSKCC Brain Tumor Center Grant
- MSKCC Center for Molecular Imaging and Nanotechnology Grant
- MSKCC Technology Development Grant
- Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research
- The Center for Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center
- Geoffrey Beene Cancer Research Center at MSKCC Grant and Shared Resources Award
- RSNA Research Scholar Grant
- Society of MSKCC Research Grant
- National Natural Science Foundation [81401461]
- R25T Molecular Imaging for Training in Oncology Program grant from the National Cancer Institute (NCI) [2R25-CA096945]
- MSKCC NIH Core Grant [P30-CA008748]
- NATIONAL CANCER INSTITUTE [K08CA163961, P30CA008748, R25CA096945] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB017748] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K08DA016396] Funding Source: NIH RePORTER
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The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors.
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