A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle

被引:851
作者
Kircher, Moritz F. [1 ,2 ,3 ,4 ]
de la Zerda, Adam [1 ,5 ]
Jokerst, Jesse V. [1 ]
Zavaleta, Cristina L. [1 ]
Kempen, Paul J. [6 ]
Mittra, Erik [1 ]
Pitter, Ken [4 ,7 ]
Huang, Ruimin [2 ,4 ,8 ]
Campos, Carl [9 ]
Habte, Frezghi [1 ]
Sinclair, Robert [6 ]
Brennan, Cameron W. [4 ,9 ,10 ,11 ]
Mellinghoff, Ingo K. [8 ,9 ,12 ]
Holland, Eric C. [4 ,7 ,8 ,10 ,11 ,13 ]
Gambhir, Sanjiv S. [1 ,6 ,14 ,15 ]
机构
[1] Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA
[3] Weill Cornell Med Coll, Dept Radiol, New York, NY USA
[4] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA
[5] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA
[6] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA
[7] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA
[8] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA
[9] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA
[10] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA
[11] Weill Cornell Med Coll, Dept Neurosurg, New York, NY USA
[12] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA
[13] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA
[14] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[15] Stanford Univ, Bio X Program, Stanford, CA 94305 USA
关键词
LIVING MICE; 5-AMINOLEVULINIC ACID; MALIGNANT GLIOMA; CARBON NANOTUBES; SPECTROSCOPY; RESECTION; FLUORESCENCE; AGENTS; SENSITIVITY; MICROSCOPY;
D O I
10.1038/nm.2721
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The difficulty in delineating brain tumor margins is a major obstacle in the path toward better outcomes for patients with brain tumors. Current imaging methods are often limited by inadequate sensitivity, specificity and spatial resolution. Here we show that a unique triple-modality magnetic resonance imaging-photoacoustic imaging-Raman imaging nanoparticle (termed here MPR nanoparticle) can accurately help delineate the margins of brain tumors in living mice both preoperatively and intraoperatively. The MPRs were detected by all three modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive tumor delineation using all three modalities through the intact skull. Raman imaging allowed for guidance of intraoperative tumor resection, and a histological correlation validated that Raman imaging was accurately delineating the brain tumor margins. This new triple-modality-nanoparticle approach has promise for enabling more accurate brain tumor imaging and resection.
引用
收藏
页码:829 / U235
页数:7
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