Molecular body imaging: MR imaging, CT, and US. Part II. Applications

Radiology

Volumn 264, Issue 2, 2012, Pages 349-368

  Kircher, Moritz F ^a   Willmann, Jürgen K ^b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEVACIZUMAB; BISMUTH SULFATE NANOPARTICLE; CARBON 13; CONTRAST MEDIUM; FERUCARBOTRAN; FERUMOXYTOL; FLUOROCARBON; FOLIC ACID; GADOLINIUM CHELATE; GADOLINIUM PENTETATE; GEMCITABINE; HIGH DENSITY LIPOPROTEIN; INTEGRIN; LIPOPROTEIN; LIPOSOME; MATRIX METALLOPROTEINASE INHIBITOR; MYELOPEROXIDASE; NANOPARTICLE; OLEIC ACID; PADGEM PROTEIN; POLYASPARTIC ACID; PROTAMINE SULFATE; STREPTAVIDIN; SUPERPARAMAGNETIC IRON OXIDE; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; ULTRASMALL SUPERPARAMAGNETIC IRON OXIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN ANTIBODY; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; ATHEROSCLEROSIS; CANCER STAGING; CELL TRACKING; COLITIS; COLON CANCER; COMPUTER ASSISTED TOMOGRAPHY; ECHOGRAPHY; HUMAN; INFLAMMATION; LIGAND BINDING; LYMPH NODE METASTASIS; MACROPHAGE; METABOLISM; MOLECULAR IMAGING; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; SKIN CARCINOMA; THROMBOGENESIS; TUMOR CELL; TUMOR VASCULARIZATION;

CONTRAST MEDIA; HUMANS; MAGNETIC RESONANCE IMAGING; MOLECULAR IMAGING; SENSITIVITY AND SPECIFICITY; TOMOGRAPHY, X-RAY COMPUTED; ULTRASONOGRAPHY;

EID: 84864354048     PISSN: 00338419     EISSN: 15271315     Source Type: Journal    
DOI: 10.1148/radiol.12111703     Document Type: Review

References (156)

1. Kircher MF, Hricak H, Larson SM. Molecular imaging for personalized cancer care. Mol Oncol 2012 Mar 10. [Epub ahead of print]
2. Gore JC, Yankeelov TE, Peterson TE, Avison MJ. Molecular imaging without radiopharmaceuticals? J Nucl Med 2009;50(6):999-1007.
3. Pysz MA, Gambhir SS, Willmann JK. Molecular imaging: current status and emerging strategies. Clin Radiol 2010;65(7):500-516.
4. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS. Molecular imaging in drug development. Nat Rev Drug Discov 2008;7(7):591-607. (Pubitemid 351927724)
5. Kircher MF, Willmann JK. Molecular body imaging: MR imaging, CT, and US. I. Principles. Radiology 2012;263(3):633-643.
6. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;348(25):2491-2499. (Pubitemid 36706536)
7. Saokar A, Braschi M, Harisinghani MG. Lymphotrophic nanoparticle enhanced MR imaging (LNMRI) for lymph node imaging. Abdom Imaging 2006;31(6):660-667. (Pubitemid 46723637)
8. Wagner S, Schnorr J, Pilgrimm H, Hamm B, Taupitz M. Monomer-coated very small superparamagnetic iron oxide particles as contrast medium for magnetic resonance imaging: preclinical in vivo characterization. Invest Radiol 2002;37(4):167-177. (Pubitemid 34259726)
9. Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ. Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 1990;175(2):494-498. (Pubitemid 20135291)
10. Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 1990;175(2):489-493. (Pubitemid 20135290)
11. Clément O, Guimaraes R, de Kerviler E, Frija G. Magnetic resonance lymphography: enhancement patterns using super-paramagnetic nanoparticles. Invest Radiol 1994;29(Suppl 2):S226-S228. (Pubitemid 24221116)
12. Guimaraes R, Clément O, Bittoun J, Carnot F, Frija G. MR lymphography with super-paramagnetic iron nanoparticles in rats: pathologic basis for contrast enhancement. AJR Am J Roentgenol 1994;162(1):201-207. (Pubitemid 24043702)
13. Deserno WM, Harisinghani MG, Taupitz M, et al. Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging. Radiology 2004;233(2): 449-456. (Pubitemid 39423804)
14. Michel SC, Keller TM, Fröhlich JM, et al. Preoperative breast cancer staging: MR imaging of the axilla with ultrasmall super-paramagnetic iron oxide enhancement. Radiology 2002;225(2):527-536. (Pubitemid 35239258)
15. Nguyen BC, Stanford W, Thompson BH, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999;10(3):468-473. (Pubitemid 29463133)
16. Pannu HK, Wang KP, Borman TL, Bluemke DA. MR imaging of mediastinal lymph nodes: evaluation using a super-paramagnetic contrast agent. J Magn Reson Imaging 2000;12(6):899-904.
17. Josephson L, Kircher MF, Mahmood U, Tang Y, Weissleder R. Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes. Bioconjug Chem 2002;13(3):554-560. (Pubitemid 34527517)
18. Kircher MF, Josephson L, Weissleder R. Ratio imaging of enzyme activity using dual wavelength optical reporters. Mol Imaging 2002;1(2):89-95.
19. Kircher MF, Weissleder R, Josephson L. A dual fluorochrome probe for imaging proteases. Bioconjug Chem 2004;15(2):242-248. (Pubitemid 38365183)
20. Ellegala DB, Leong-Poi H, Carpenter JE, et al. Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation 2003;108(3):336-341. (Pubitemid 36899026)
21. Lijowski M, Caruthers S, Hu G, et al. High sensitivity: high-resolution SPECT-CT/MR molecular imaging of angiogenesis in the Vx2 model. Invest Radiol 2009;44(1):15-22.
22. Schmieder AH, Winter PM, Caruthers SD, et al. Molecular MR imaging of melanoma angiogenesis with alphanubeta3-targeted paramagnetic nanoparticles. Magn Reson Med 2005;53(3):621-627. (Pubitemid 40332283)
23. Winter PM, Caruthers SD, Kassner A, et al. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 2003;63(18):5838-5843. (Pubitemid 37187482)
24. Boles KS, Schmieder AH, Koch AW, et al. MR angiogenesis imaging with Robo4- vs alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB J 2010;24(11):4262-4270.
25. Lee HY, Li Z, Chen K, et al. PET/MRI dualmodality tumor imaging using arginineglycine- aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles. J Nucl Med 2008;49(8):1371-1379.
26. Weissleder R, Moore A, Mahmood U, et al. In vivo magnetic resonance imaging of transgene expression. Nat Med 2000;6(3):351-355.
27. Su SL, Huang IP, Fair WR, Powell CT, Heston WD. Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression. Cancer Res 1995;55(7):1441-1443.
28. Serda RE, Adolphi NL, Bisoffi M, Sillerud LO. Targeting and cellular trafficking of magnetic nanoparticles for prostate cancer imaging. Mol Imaging 2007;6(4):277-288. (Pubitemid 47509832)
29. Salazar MD, Ratnam M. The folate receptor: what does it promise in tissue-targeted therapeutics? Cancer Metastasis Rev 2007;26(1):141-152. (Pubitemid 46452188)
30. Hartmann LC, Keeney GL, Lingle WL, et al. Folate receptor overexpression is associated with poor outcome in breast cancer. Int J Cancer 2007;121(5):938-942. (Pubitemid 47101628)
31. Choi H, Choi SR, Zhou R, Kung HF, Chen IW. Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery. Acad Radiol 2004;11(9):996-1004. (Pubitemid 39220809)
32. Corot C, Robert P, Lancelot E, et al. Tumor imaging using P866, a high-relaxivity gadolinium chelate designed for folate receptor targeting. Magn Reson Med 2008;60(6):1337-1346.
33. Konda SD, Aref M, Brechbiel M, Wiener EC. Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor: work in progress. Invest Radiol 2000;35(1):50-57. (Pubitemid 30033607)
34. Meier R, Henning TD, Boddington S, et al. Breast cancers: MR imaging of folatereceptor expression with the folate-specific nanoparticle P1133. Radiology 2010;255(2):527-535.
35. Swanson SD, Kukowska-Latallo JF, Patri AK, et al. Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement. Int J Nanomedicine 2008;3(2):201-210. (Pubitemid 352037852)
36. Wang ZJ, Boddington S, Wendland M, Meier R, Corot C, Daldrup-Link H. MR imaging of ovarian tumors using folate-receptor-targeted contrast agents. Pediatr Radiol 2008;38(5):529-537.
37. Libby P. Inflammation in atherosclerosis. Nature 2002;420(6917):868-874. (Pubitemid 36019640)
38. Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009;54(23):2129-2138.
39. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105(9):1135-1143. (Pubitemid 34212626)
40. Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation 2001;103(3):415-422. (Pubitemid 32105982)
41. Schmitz SA, Coupland SE, Gust R, et al. Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits. Invest Radiol 2000;35(8):460-471. (Pubitemid 30622013)
42. Morishige K, Kacher DF, Libby P, et al. High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis. Circulation 2010;122(17):1707-1715.
43. Schmitz SA, Taupitz M, Wagner S, Wolf KJ, Beyersdorff D, Hamm B. Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. J Magn Reson Imaging 2001;14(4):355-361. (Pubitemid 32906552)
44. Tang TY, Patterson AJ, Miller SR, et al. Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques. Neuroradiology 2009;51(7):457-465.
45. Trivedi RA, Mallawarachi C, U-King-Im JM, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol 2006;26(7):1601-1606. (Pubitemid 44288989)
46. Amirbekian V, Lipinski MJ, Briley-Saebo KC, et al. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci U S A 2007;104(3):961-966. (Pubitemid 46154719)
47. Amirbekian V, Aguinaldo JG, Amirbekian S, et al. Atherosclerosis and matrix metal-loproteinases: experimental molecular MR imaging in vivo. Radiology 2009;251(2):429-438.
48. Cybulsky MI, Gimbrone MA Jr. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991;251(4995):788- 791.
49. Nahrendorf M, Jaffer FA, Kelly KA, et al. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 2006;114(14):1504-1511. (Pubitemid 44527006)
50. Nahrendorf M, Zhang H, Hembrador S, et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 2008;117(3):379-387.
51. Skajaa T, Cormode DP, Falk E, Mulder WJ, Fisher EA, Fayad ZA. High-density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis. Arterioscler Thromb Vasc Biol 2010;30(2):169-176.
52. Cormode DP, Skajaa T, van Schooneveld MM, et al. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. Nano Lett 2008;8(11):3715-3723.
53. Frias JC, Williams KJ, Fisher EA, Fayad ZA. Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 2004; 126(50):16316-16317. (Pubitemid 40081918)
54. Lanza GM, Winter PM, Caruthers SD, et al. Nanomedicine opportunities for cardiovascular disease with perfluorocarbon nanoparticles. Nanomedicine (Lond) 2006;1(3):321-329.
55. Winter PM, Morawski AM, Caruthers SD, et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v) beta3-integrin- targeted nanoparticles. Circulation 2003;108(18):2270-2274. (Pubitemid 37363046)
56. Chen JW, Querol Sans M, Bogdanov A Jr, Weissleder R. Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 2006;240(2):473-481. (Pubitemid 44098644)
57. Ronald JA, Chen JW, Chen Y, et al. Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation 2009;120(7):592-599.
58. Cunningham CH, Chen AP, Albers MJ, et al. Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C. J Magn Reson 2007;187(2):357-362. (Pubitemid 47069025)
59. Larson PE, Kerr AB, Chen AP, et al. Multiband excitation pulses for hyperpolarized 13C dynamic chemical-shift imaging. J Magn Reson 2008;194(1):121-127.
60. Levin YS, Mayer D, Yen YF, Hurd RE, Spielman DM. Optimization of fast spiral chemical shift imaging using least squares reconstruction: application for hyperpolarized (13)C metabolic imaging. Magn Reson Med 2007;58(2):245-252. (Pubitemid 47267641)
61. Reeder SB, Brittain JH, Grist TM, Yen YF. Least-squares chemical shift separation for (13)C metabolic imaging. J Magn Reson Imaging 2007;26(4):1145-1152. (Pubitemid 47548181)
62. Albers MJ, Bok R, Chen AP, et al. Hyper-polarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res 2008;68(20):8607-8615.
63. Chen AP, Albers MJ, Cunningham CH, et al. Hyperpolarized C-13 spectroscopic imaging of the TRAMP mouse at 3T-initial experience. Magn Reson Med 2007;58(6):1099-1106. (Pubitemid 350234196)
64. Day SE, Kettunen MI, Gallagher FA, et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 2007;13(11):1382-1387. (Pubitemid 350073590)
65. Golman K, Petersson JS, Magnusson P, et al. Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med 2008;59(5):1005-1013. (Pubitemid 351590513)
66. Golman K, Zandt RI, Lerche M, Pehrson R, Ardenkjaer-Larsen JH. Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. Cancer Res 2006;66(22):10855-10860. (Pubitemid 44876982)
67. Kohler SJ, Yen Y, Wolber J, et al. In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate. Magn Reson Med 2007;58(1):65-69. (Pubitemid 47229918)
68. Merritt ME, Harrison C, Storey C, Jeffrey FM, Sherry AD, Malloy CR. Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc Natl Acad Sci U S A 2007;104(50):19773-19777.
69. Merritt ME, Harrison C, Storey C, Sherry AD, Malloy CR. Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3-.Magn Reson Med 2008;60(5):1029-1036.
70. Nelson SJ, Vigneron D, Kurhanewicz J, Chen A, Bok R, Hurd R. DNP-hyperpolarized C magnetic resonance metabolic imaging for cancer applications. Appl Magn Reson 2008;34(3-4):533-544.
71. Schroeder MA, Atherton HJ, Cochlin LE, Clarke K, Radda GK, Tyler DJ. The effect of hyperpolarized tracer concentration on myocardial uptake and metabolism. Magn Reson Med 2009;61(5):1007-1014.
72. Schroeder MA, Cochlin LE, Heather LC, Clarke K, Radda GK, Tyler DJ. In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci U S A 2008;105(33):12051- 12056.
73. Viale A, Aime S. Current concepts on hyperpolarized molecules in MRI. Curr Opin Chem Biol 2010;14(1):90-96.
74. Gallagher FA, Kettunen MI, Day SE, et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature 2008;453(7197):940-943. (Pubitemid 351832568)
75. Chen AP, Kurhanewicz J, Bok R, et al. Feasibility of using hyperpolarized [1-13C]lactate as a substrate for in vivo metabolic 13C MRSI studies. Magn Reson Imaging 2008;26(6):721-726.
76. Gallagher FA, Kettunen MI, Day SE, Lerche M, Brindle KM. 13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine. Magn Reson Med 2008;60(2):253-257.
77. Gabellieri C, Reynolds S, Lavie A, Payne GS, Leach MO, Eykyn TR. Therapeutic target metabolism observed using hyperpolarized 15N choline. J Am Chem Soc 2008;130(14):4598-4599. (Pubitemid 351500092)
78. Chekmenev EY, Hövener J, Norton VA, et al. PASADENA hyperpolarization of succinic acid for MRI and NMR spectroscopy. J Am Chem Soc 2008;130(13):4212-4213. (Pubitemid 351466399)
79. Kircher MF, Gambhir SS, Grimm J. Noninvasive cell-tracking methods. Nat Rev Clin Oncol 2011;8(11):677-688.
80. Grimm J, Kircher MF, Weissleder R. Cell tracking: principles and applications [in German]. Radiologe 2007;47(1):25-33.
81. Bulte JW. In vivo MRI cell tracking: clinical studies. AJR Am J Roentgenol 2009;193(2):314-325.
82. Frank JA, Miller BR, Arbab AS, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 2003;228(2):480-487. (Pubitemid 36910091)
83. de Vries IJ, Lesterhuis WJ, Barentsz JO, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 2005;23(11):1407-1413. (Pubitemid 41679393)
84. Saudek F, Jirák D, Girman P, et al. Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans. Transplantation 2010;90(12):1602-1606.
85. Moore A, Weissleder R, Bogdanov A Jr. Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages. J Magn Reson Imaging 1997;7(6):1140-1145. (Pubitemid 28372892)
86. Bulte JW, Kraitchman DL. Monitoring cell therapy using iron oxide MR contrast agents. Curr Pharm Biotechnol 2004;5(6):567-584. (Pubitemid 39654853)
87. Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004;17(7):513-517. (Pubitemid 39549429)
88. Montet-Abou K, Montet X, Weissleder R, Josephson L. Transfection agent induced nanoparticle cell loading. Mol Imaging 2005;4(3):165-171. (Pubitemid 43143789)
89. Ahrens ET, Feili-Hariri M, Xu H, Genove G, Morel PA. Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med 2003;49(6):1006-1013. (Pubitemid 36627278)
90. Bulte JW, Zhang S, van Gelderen P, et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A 1999;96(26):15256- 15261. (Pubitemid 30019799)
91. Kircher MF, Allport JR, Graves EE, et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic Tlymphocyte trafficking to tumors. Cancer Res 2003;63(20):6838-6846. (Pubitemid 37322966)
92. Kircher MF, Allport JR, Zhao M, Josephson L, Lichtman AH, Weissleder R. Intracellular magnetic labeling with CLIO-Tat for efficient in vivo tracking of cytotoxic T cells by MR imaging [abstr]. Radiology 2002;225(P):453.
93. Bulte JW, Douglas T, Witwer B, et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 2001;19(12):1141-1147. (Pubitemid 33115700)
94. Aung W, Hasegawa S, Koshikawa-Yano M, et al. Visualization of in vivo electroporation-mediated transgene expression in experimental tumors by optical and magnetic resonance imaging. Gene Ther 2009;16(7):830-839.
95. Hasegawa S, Furukawa T, Saga T. Molecular MR imaging of cancer gene therapy: ferritin transgene reporter takes the stage. Magn Reson Med Sci 2010;9(2):37-47.
96. Suzuki Y, Zhang S, Kundu P, Yeung AC, Robbins RC, Yang PC. In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 2007;57(6):1173-1179. (Pubitemid 46911301)
97. Ahrens ET, Flores R, Xu H, Morel PA. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 2005; 23(8):983-987. (Pubitemid 41114032)
98. Partlow KC, Chen J, Brant JA, et al. 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J 2007;21(8):1647-1654. (Pubitemid 46855610)
99. Ward KM, Aletras AH, Balaban RS. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 2000;143(1):79-87.
100. Bogdanov A Jr, Matuszewski L, Bremer C, Petrovsky A, Weissleder R. Oligomerization of paramagnetic substrates result in signal amplification and can be used for MR imaging of molecular targets. Mol Imaging 2002;1(1):16-23.
101. Grimm J, Perez JM, Josephson L, Weissleder R. Novel nanosensors for rapid analysis of telomerase activity. Cancer Res 2004;64(2):639-643. (Pubitemid 38120904)
102. Perez JM, Josephson L, O'Loughlin T, Högemann D, Weissleder R. Magnetic relaxation switches capable of sensing molecular interactions. Nat Biotechnol 2002; 20(8):816-820. (Pubitemid 34836759)
103. Perez JM, Simeone FJ, Saeki Y, Josephson L, Weissleder R. Viral-induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media. J Am Chem Soc 2003;125(34):10192-10193. (Pubitemid 37022228)
104. Morawski AM, Winter PM, Crowder KC, et al. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 2004;51(3):480-486. (Pubitemid 38298660)
105. Aime S, Carrera C, Delli Castelli D, Geninatti Crich S, Terreno E. Tunable imaging of cells labeled with MRI-PARACEST agents. Angew Chem Int Ed Engl 2005;44(12):1813-1815.
106. Louie AY, Hüber MM, Ahrens ET, et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 2000;18(3):321-325. (Pubitemid 30159486)
107. Kircher MF, Mahmood U, King RS, Weissleder R, Josephson L. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res 2003;63(23):8122-8125. (Pubitemid 37549457)
108. Nahrendorf M, Sosnovik D, Chen JW, et al. Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury. Circulation 2008;117(9):1153-1160. (Pubitemid 351552019)
109. Kircher MF, de la Zerda A, Jokerst JV, et al. A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle. Nat Med 2012 Apr 15. [Epub ahead of print]
110. Rabin O, Manuel Perez J, Grimm J, Wojtkiewicz G, Weissleder R. An x-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater 2006;5(2):118-122. (Pubitemid 43177900)
111. Hyafil F, Cornily JC, Feig JE, et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med 2007;13(5):636-641. (Pubitemid 46828482)
112. Jackson PA, Rahman WN, Wong CJ, Ackerly T, Geso M. Potential dependent superiority of gold nanoparticles in comparison to iodinated contrast agents. Eur J Radiol 2010;75(1):104-109.
113. Aydogan B, Li J, Rajh T, et al. AuNP-DG: deoxyglucose-labeled gold nanoparticles as x-ray computed tomography contrast agents for cancer imaging. Mol Imaging Biol 2010;12(5):463-467.
114. Popovtzer R, Agrawal A, Kotov NA, et al. Targeted gold nanoparticles enable molecular CT imaging of cancer. Nano Lett 2008;8(12):4593-4596.
115. Cormode DP, Roessl E, Thran A, et al. Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles. Radiology 2010;256(3):774-782.
116. Frangioni JV, Hajjar RJ. In vivo tracking of stem cells for clinical trials in cardiovascular disease. Circulation 2004;110(21):3378-3383. (Pubitemid 39557503)
117. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003;17(5):545-580. (Pubitemid 36307540)
118. Klibanov AL, Rasche PT, Hughes MS, et al. Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles. Invest Radiol 2004;39(3):187-195. (Pubitemid 38263925)
119. Deshpande N, Ren Y, Foygel K, Rosenberg J, Willmann JK. Tumor angiogenic marker expression levels during tumor growth: longitudinal assessment with molecularly targeted microbubbles and US imaging. Radiology 2011;258(3):804-811.
120. Tardy I, Pochon S, Theraulaz M, et al. Ultrasound molecular imaging of VEGFR2 in a rat prostate tumor model using BR55. Invest Radiol 2010;45(10):573-578.
121. Fischer T, Thomas A, Tardy I, et al. Vascular endothelial growth factor receptor 2-specific microbubbles for molecular ultrasound detection of prostate cancer in a rat model. Invest Radiol 2010;45(10):675-684.
122. Pysz MA, Foygel K, Rosenberg J, Gambhir SS, Schneider M, Willmann JK. Antiangiogenic cancer therapy: monitoring with molecular US and a clinically translatable contrast agent (BR55). Radiology 2010;256(2):519-527.
123. Pochon S, Tardy I, Bussat P, et al. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol 2010;45(2):89-95.
124. Willmann JK, Kimura RH, Deshpande N, Lutz AM, Cochran JR, Gambhir SS. Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med 2010;51(3):433-440.
125. Willmann JK, Lutz AM, Paulmurugan R, et al. Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 2008;248(3):936-944.
126. Willmann JK, Paulmurugan R, Chen K, et al. US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 2008;246(2):508-518.
127. Lee DJ, Lyshchik A, Huamani J, Hallahan DE, Fleischer AC. Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultra-sonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model. J Ultrasound Med 2008;27(6):855-866. (Pubitemid 351913824)
128. Rychak JJ, Graba J, Cheung AM, et al. Microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis. Mol Imaging 2007;6(5):289-296. (Pubitemid 350013534)
129. Weller GE, Wong MK, Modzelewski RA, et al. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res 2005;65(2):533-539.
130. Deshpande N, Lutz AM, Ren Y, et al. Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US. Radiology 2012;262(1):172-180.
131. Kaufmann BA, Carr CL, Belcik JT, et al. Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease. Arterioscler Thromb Vasc Biol 2010;30(1):54-59.
132. Kaufmann BA, Sanders JM, Davis C, et al. Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation 2007;116(3):276-284. (Pubitemid 47196563)
133. Villanueva FS, Lu E, Bowry S, et al. Myocardial ischemic memory imaging with molecular echocardiography. Circulation 2007;115(3):345-352. (Pubitemid 46151660)
134. Bachmann C, Klibanov AL, Olson TS, et al. Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology 2006;130(1):8-16. (Pubitemid 43049830)
135. Kondo I, Ohmori K, Oshita A, et al. Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model. Circulation 2004;109(8):1056-1061. (Pubitemid 38282861)
136. Leong-Poi H, Christiansen J, Klibanov AL, Kaul S, Lindner JR. Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 2003;107(3):455-460. (Pubitemid 36158049)
137. Weller GE, Lu E, Csikari MM, et al. Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1. Circulation 2003;108(2):218-224. (Pubitemid 36871306)
138. Wang B, Zang WJ, Wang M, et al. Prolonging the ultrasound signal enhancement from thrombi using targeted microbubbles based on sulfur-hexafluoride-filled gas. Acad Radiol 2006;13(4):428-433.
139. Schumann PA, Christiansen JP, Quigley RM, et al. Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi. Invest Radiol 2002;37(11):587-593. (Pubitemid 35231692)
140. Kaufmann BA, Lewis C, Xie A, Mirza-Mohd A, Lindner JR. Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography. Eur Heart J 2007;28(16):2011-2017. (Pubitemid 47591499)
141. Deshpande N, Needles A, Willmann JK. Molecular ultrasound imaging: current status and future directions. Clin Radiol 2010;65(7):567-581.
142. Pysz MA, Willmann JK. Targeted contrast-enhanced ultrasound: an emerging technology in abdominal and pelvic imaging. Gastroenterology 2011;140(3):785-790.
143. Ferrante EA, Pickard JE, Rychak J, Klibanov A, Ley K. Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release 2009;140(2):100-107.
144. Pysz MA, Guracar I, Foygel K, Tian L, Willmann JK. Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging. Angiogenesis 2012 Apr 26. [Epub ahead of print]
145. Willmann JK, Cheng Z, Davis C, et al. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice. Radiology 2008;249(1):212-219.
146. Deshpande N, Pysz MA, Willmann JK. Molecular ultrasound assessment of tumor angiogenesis. Angiogenesis 2010;13(2):175-188.
147. Palmowski M, Huppert J, Ladewig G, et al. Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Mol Cancer Ther 2008;7(1):101-109.
148. Korpanty G, Carbon JG, Grayburn PA, Fleming JB, Brekken RA. Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 2007;13(1):323-330. (Pubitemid 46121886)
149. Lyshchik A, Fleischer AC, Huamani J, Hallahan DE, Brissova M, Gore JC. Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography. J Ultrasound Med 2007;26(11):1575-1586. (Pubitemid 351519803)
150. Marshall D, Pedley RB, Boden JA, Boden R, Melton RG, Begent RH. Polyethylene glycol modification of a galactosylated streptavidin clearing agent: effects on immunogenicity and clearance of a biotinylated anti-tumour antibody. Br J Cancer 1996;73(5):565-572. (Pubitemid 26068858)
151. Meyer DL, Schultz J, Lin Y, et al. Reduced antibody response to streptavidin through site-directed mutagenesis. Protein Sci 2001;10(3):491-503. (Pubitemid 32221140)
152. Kaufmann BA. Ultrasound molecular imaging of atherosclerosis. Cardiovasc Res 2009;83(4):617-625.
153. Klibanov AL. Preparation of targeted microbubbles: ultrasound contrast agents for molecular imaging. Med Biol Eng Comput 2009;47(8):875-882.
154. Zavaleta CL, Kircher MF, Gambhir SS. Raman's "effect" on molecular imaging. J Nucl Med 2011;52(12):1839-1844.
155. Hoffman JM, Gambhir SS, Kelloff GJ. Regulatory and reimbursement challenges for molecular imaging. Radiology 2007;245(3):645-660. (Pubitemid 350139065)
156. Nunn AD. The cost of developing imaging agents for routine clinical use. Invest Radiol 2006;41(3):206-212. (Pubitemid 44406180)