Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles and Their Curative Effect on the Tumor Microenvironment

• Published in: Contrast media and molecular imaging Vol. 2017; pp. 3849373 - 15
• Main Authors: Maritim, Samuel, Coman, Daniel, Huang, Yuegao, Rao, Jyotsna U., Walsh, John J., Hyder, Fahmeed
• Format: Journal Article
• Language: English
• Published: England Hindawi 01.01.2017; Hindawi Limited
• Subjects: Animals; Biosensors; Bird strike tests; Birds; Brain; Brain cancer; Brain mapping; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain tumors; Cancer therapies; Contrast agents; Contrast Media - chemistry; Contrast Media - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug delivery; Drug delivery systems; Drug dosages; Drugs; Glioma; Glioma - diagnostic imaging; Glioma - drug therapy; Hydrogen-Ion Concentration; Injection; Intravenous administration; Iron oxides; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - therapeutic use; Male; Mapping; Medical prognosis; Metabolism; Metabolites; Microvasculature; Nanoparticles; Neuroimaging; NMR; Nuclear magnetic resonance; Payloads; Permeability; pH effects; Protons; Rats; Rats, Inbred F344; Tumor Microenvironment; Tumors
• ISSN: 1555-4309; 1555-4317
• DOI: 10.1155/2017/3849373

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH (pHe) is a tumor hallmark, mapping pHe is critical. Brain pHe is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based pHe readout remains uncompromised by presence of SPIO-NPs, we mapped pHe in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the pHe inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based pHe can map their therapeutic impact.