New approaches for imaging tumour responses to treatment

Nature Reviews Cancer

Volumn 8, Issue 2, 2008, Pages 94-107

  Brindle, Kevin ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b CANCER RESEARCH UK CAMBRIDGE RESEARCH INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; FLUORODEOXYGLUCOSE; GEFITINIB; GLUCOSE TRANSPORTER 1; IMATINIB; SOMATOSTATIN DERIVATIVE;

AMINO ACID METABOLISM; ASTROCYTOMA; BREAST CANCER; CANCER CELL CULTURE; CANCER DIAGNOSIS; CARBON NUCLEAR MAGNETIC RESONANCE; COMPUTER ASSISTED TOMOGRAPHY; DNA SYNTHESIS; DRUG EFFICACY; ESOPHAGEAL ADENOCARCINOMA; FLUORINE NUCLEAR MAGNETIC RESONANCE; GASTROINTESTINAL STROMAL TUMOR; GLYCOLYSIS; HUMAN; LIPID METABOLISM; LUNG CANCER; LYMPHOMA; MOLECULAR IMAGING; NONHUMAN; OPTICAL COHERENCE TOMOGRAPHY; OVARY CANCER; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; TREATMENT RESPONSE; TUMOR VOLUME;

ANIMALS; CLINICAL TRIALS AS TOPIC; DIAGNOSTIC IMAGING; FLUORODEOXYGLUCOSE F18; GLYCOLYSIS; HUMANS; MAGNETIC RESONANCE IMAGING; MAGNETIC RESONANCE SPECTROSCOPY; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; POSITRON-EMISSION TOMOGRAPHY; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON; TOMOGRAPHY, X-RAY COMPUTED; ULTRASONOGRAPHY;

EID: 38549166422     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2289     Document Type: Review

References (142)

1. Paez, J. G. et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004).
2. Sotiriou, C. & Piccart, M. J. Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Nature Rev. Cancer 7, 545-553 (2007).
3. Galbraith, S. M. et al. Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. J. Clin. Oncol. 21, 2831-2842 (2003).
4. Therasse, P. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst. 92, 205-216 (2000).
5. Michaelis, L. C. & Ratain, M. J. Measuring response in a post-RECIST world: from black and white to shades of grey. Nature Rev. Cancer 6, 409-414 (2006).
6. Weissleder, R. & Mahmood, U. Molecular imaging. Radiology 219, 316-333 (2001). A relatively early review from a pioneer (R.W.) of the field of molecular imaging.
7. Weissleder, R. Scaling down imaging: molecular mapping of cancer in mice. Nature Rev. Cancer 2, 1-8 (2001).
8. Boone, J. M., Velazquez, O. & Cherry, S. R. Small-animal X-ray dose from micro-CT. Mol. Imaging 3, 149-158 (2004).
9. von Schulthess, G. K., Steinert, H. C. & Hany, T. F. Integrated PET/CT: Current applications and future directions. Radiology 238, 405-422 (2006).
10. Gee, M. S. et al. Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations. Cancer Res. 61, 2974-2982 (2001).
11. Czarnota, G. J. et al. Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo. Br. J. Cancer 81, 520-527 (1999).
12. Pellot-Barakat, C., Sridhar, M., Lindfors, K. K. & Insana, M. F. Ultrasonic elasticity imaging as a tool for breast cancer diagnosis and research. Curr. Med. Imaging Rev. 2, 157-164 (2006).
13. Sinkus, R. et al. High-resolution tensor MR elastography for breast tumour detection. Phys. Med. Biol. 45, 1649-1664 (2000).
14. Kaufmann, B. A. & Lindner, J. R. Molecular imaging with targeted contrast ultrasound. Curr. Opin. Biotechnol. 18, 11-16 (2007).
15. Johnson, G. A., Cofer, G., Gewalt, S. L. & Hedlund, L. W. Morphologic phenotyping with MR microscopy: The visible mouse. Radiology 222, 789-793 (2002).
16. Artemov, D., Mori, N., Ravi, R. & Bhujwalla, Z. M. Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res. 63, 2723-2727 (2003).
17. 3-targeted magnetic resonance imaging. Nature Med. 4, 623-626 (1998). A relatively early and much cited example of receptor imaging using MRI. A forerunner of later attempts to image angiogenesis using MRI.
18. 3-targeted nanoparticle and 1.5 Tesla magnetic resonance imaging. Cancer Res. 63, 5838-5843 (2003).
19. Zhao, M., Beauregard, D. A., Loizou, L., Davletov, B. & Brindle, K. M. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nature Med. 7, 1241-1244 (2001).
20. Schellenberger, E. A. et al. Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Mol. Imaging 1, 102-107 (2002).
21. Jung, H. I., Kettunen, M. I., Davletov, B. & Brindle, K. M. Detection of apoptosis using the C2A domain of synaptotagmin, I. Bioconjug. Chem. 15, 983-987 (2004).
22. Bulte, J. W. M. & Kraitchman, D. L. Monitoring cell therapy using iron oxide MR contrast agents. Curr. Pharm. Biotech. 5, 567-584 (2004).
23. Aime, S., Barge, A., Cabella, C., Crich, S. G. & Gianolio, E. Targeting cells with MR imaging probes based on paramagnetic Gd(III) chelates. Curr. Pharm. Biotech. 5, 509-518 (2004).
24. Dodd, S. J. et al. Detection of single mammalian cells by high resolution magnetic resonance imaging. Biophys. J. 76, 103-109 (1999).
25. Franklin, R. J. M. et al. Magnetic resonance imaging of transplanted oligodendrocyte precursors in the rat brain. NeuroReport 10, 1-5 (1999).
26. Bulte, J. W. M. et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination. Proc. Natl Acad. Sci. USA 96, 15256-15261 (1999).
27. Kircher, M. F. et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res. 63, 6838-6846 (2003).
28. Hu, D.-E., Kettunen, M. I. & Brindle, K. M. Monitoring T-lymphocyte trafficking in tumors undergoing immune rejection. Magn. Reson. Med. 54, 1473-1479 (2005).
29. de Vries, I. J. M. et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nature Biotech. 23, 1407-1413 (2005).
30. Ahrens, E. T., Flores, R., Xu, H. Y. & Morel, P. A. In vivo imaging platform for tracking immunotherapeutic cells. Nature Biotech. 23, 983-987 (2005).
31. Preul, M. C. et al. Accurate, non-invasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nature Med. 2, 232-325 (1996). An early example of the use of MRS and pattern-recognition techniques to classify brain tumours.
32. Tate, A. R. et al. Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. NMR Biomed. 19, 411-434 (2006).
33. Gillies, R. J. & Morse, D. L. In vivo magnetic resonance spectroscopy in cancer. Ann. Rev. Biomed. Bioeng. 7, 287-326 (2005).
34. 13C- labeling techniques, particularly with multiply labeled compounds, for interrogating cellular metabolism.
35. Golman, K., Ardenkjær-Larsen, J. H., Petersson, J. S., Månsson, S. & Leunbach, I. Molecular imaging with endogenous substances. Proc. Natl Acad. Sci. USA 100, 10435-10439 (2003).
36. Golman, K., in 't Zandt, R. & Thaning, M. Real-time metabolic imaging. Proc. Natl Acad. Sci. USA 103, 11270-11275 (2006).
37. 13C magnetic resonance imaging for in vivo tumor diagnosis. Cancer Res. 66, 10855-10860 (2006).
38. 13C. Acad. Radiol. 13, 932-942 (2006).
39. Gambhir, S. S. Molecular imaging of cancer with positron emisson tomography. Nature Rev. Cancer 2, 683-693 (2002).
40. Folli, S. et al. Antibody-indocyanin conjugates for immunophotodetection of human squamous cell carcinoma in nude mice. Cancer Res. 54, 2643-2649 (1994).
41. Becker, A. et al. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nature Biotech. 19, 327-331 (2001). A good example of using a targeted optical agent for tumour detection.
42. Kelly, K., Alencar, H., Funovics, M., Mahmood, U. & Weissleder, R. Detection of invasive colon cancer using a novel, targeted, library-derived fluorescent peptide. Cancer Res. 64, 6247-6251 (2004).
43. Weissleder, R., Tung, C.-H., Mahmood, U. & Bogdanov, A. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nature Biotech. 17, 375-378 (1999). A classic and much cited example of a molecular beacon for measuring tumour-associated protease activity.
44. Alencar, H. et al. Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection - study in mice. Radiology 244, 232-238 (2007).
45. Ntziachristos, V., Yodh, A. G., Schnall, M. & Chance, B. Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement. Proc. Natl Acad. Sci. USA 97, 2767-2772 (2000). A paper that describes NIR imaging in the human.
46. Inoue, H., Kudo, S.-e. & Shiokawa, A. Technology Insight: laser scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract. Nature Clin. Prac. Gasteroenterol. Hepatol. 2, 31-37 (2005).
47. Yun, S. H. et al. Comprehensive volumetric optical microscopy in vivo. Nature Med. 12, 1429-1433 (2006).
48. Boppart, S. A., Oldenburg, A. L., Xu, C. Y. & Marks, D. L. Optical probes and techniques for molecular contrast enhancement in coherence imaging. J. Biomed. Optics 10, 041208 (2005).
49. Kendall, C. et al. Raman spectroscopy, a potential tool for the objective identification and classification of neoplasia in Barrett's oesophagus. J. Pathol. 200, 602-609 (2003).
50. Short, K. W., Carpenter, S., Freyer, J. P. & Mourant, J. R. Raman spectroscopy detects biochemical changes due to proliferation in mammalian cell cultures. Biophys. J. 88, 4274-4288 (2005).
51. Massoud, T. F. & Gambhir, S. S. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 17, 545-580 (2003). An encyclopaedic review from another pioneer (S.S.G.) in the field of molecular imaging.
52. Bhaumik, S. & Gambhir, S. S. Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc. Natl Acad. Sci. USA 99, 377-382 (2002).
53. Hardy, J. et al. Bioluminescence imaging of lymphocyte trafficking in vivo. Exp. Hematol. 29, 1353-1360 (2001).
54. Sweeney, T. J. et al. Visualizing the kinetics of tumorcell clearance in living animals. Proc. Natl Acad. Sci. USA 96, 12044-12049 (1999).
55. Vooijs, M., Jonkers, J., Lyons, S. & Berns, A. Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res. 62, 1862-1867 (2002). An elegant example of how to detect early-stage tumours in a mouse model using bioluminescent imaging.
56. Gatenby, R. A. & Gillies, R. J. Why do cancers have high aerobic glycolysis? Nature Rev. Cancer 4, 891-899 (2004).
57. Brown, R., Leung, J. & Fisher, S. Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J. Nucl. Med. 37, 1042-1047 (1996).
58. 18F]fluoro- 2-deoxy-D-glucose (FDG) incorporation. Nucl. Med. Biol. 28, 1-4 (2001).
59. Juweid, M. E. & Cheson, B. D. Positron-emission tomography and assessment of cancer therapy. N. Engl. J. Med. 354, 496-507 (2006).
60. Weber, W.A et al. Positron emission tomography in non-small-cell lung cancer: Prediction of response to chemotherapy by quantitative assessment of glucose use. J. Clin. Oncol. 21, 2651-2657 (2003).
61. Weber, W. A. et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J. Clin. Oncol. 19, 3058-3065 (2001).
62. 18F]FDG PET a valid alternative to conventional diagnostic methods? J. Clin. Oncol. 19, 414-419 (2001).
63. 18F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J. Clin. Oncol. 18, 1689-1695 (2000).
64. Avril, N. et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J. Clin. Oncol. 23, 7445-7453 (2005).
65. 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur. J. Cancer 39, 2012-2020 (2003). A well-known example of how FDG PET can detect response before changes in tumour size.
66. Cullinane, C. et al. An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res. 65, 9633-9636 (2005).
67. Su, H. et al. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin. Cancer Res. 12, 5659-5667 (2006).
68. Weber, W. A. Positron emission tomography as an imaging biomarker. J. Clin. Oncol. 24, 3282-3292 (2006). A recent and well-written review of the role of PET in oncology.
69. Poptani, H. et al. Detecting early response to cyclophosphamide treatment of RIF-1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging. NMR Biomed. 16, 102-111 (2003).
70. Ardenkjaer-Larsen, J. H. et al. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc. Natl Acad. Sci. USA 100, 10158-10163 (2003). The first description of dissolution dynamic nuclear polarization, a technique that could have an enormous effect on imaging tissue function using magnetic resonance.
71. 13C magnetic resonance imaging and spectroscopy. Nature Med. 13, 1382-1387 (2007). The first example of the use of hyperpolarized magnetic resonance spectroscopic imaging to detect the response of tumours to therapy.
72. Shields, A. F. et al. Carbon-11-thymidine and FDG to measure therapy response. J. Nucl. Med. 39, 1757-1762 (1998).
73. 11C]thymidine positron emission tomography in advanced intra-abdominal malignancies. Cancer Res. 62, 5698-5702 (2002).
74. 18F]FLT and positron emission tomography. Nature Med. 11, 1334-1336 (1998). The first description of FLT as a PET probe of cell proliferation.
75. 18F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin. Cancer Res. 8, 3315-3323 (2002).
76. 18F]fluoro- 3′-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol. Imaging Biol. 8, 36-42 (2006).
77. an Waarde, A., Been, L. B., Ishiwata, K., Dierckx, R. A. & Elsinga, P. H. Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy: an in vitro study in glioma cells. J. Nucl. Med. 47, 1538-1545 (2006).
78. Jager, P. L. et al. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J. Nucl. Med. 42, 432-445 (2001).
79. 11C]methionine-positron emission tomography. Radiother. Oncol. 52, 225-232 (1999).
80. 11C]methyl- L-methionine for therapy monitoring in patients with rectal cancer. Eur. J. Nuc. Med. Mol. Imaging 29, 789-796 (2002).
81. 11C- methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy. Ann. Nucl. Med. 18, 669-674 (2004).
82. 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur. J. Nuc. Med. Mol. Imaging 33, 516-524 (2006).
83. 11C]methionine pet in patients with low-grade astrocytoma. Int. J. Radiat. Oncol. Biol. Phys. 48, 43-52 (2000).
84. Yoshimoto, M. et al. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells. Nucl. Med. Biol. 28, 117-122 (2001).
85. Jana, S. & Blaufox, M. D. Nuclear medicine studies of the prostate, testes, and bladder. Semin. Nucl. Med. 36, 51-72 (2006).
86. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J. Nucl. Med. 44, 549-555 (2003).
87. Glunde, K., Jacobs, M. A. & Bhujwalla, Z. M. Choline metabolism in cancer: implications for diagnosis and therapy. Expert Rev. Mol. Diag. 6, 821-829 (2006). A recent review of the role of choline metabolism in tumour cell proliferation and different ways of imaging this from a group that has been very active in this field.
88. 1H MR spectroscopy - A pilot study. Radiology 233, 424-431 (2004).
89. Kurhanewicz, J., Vigneron, D. B. & Nelson, S. J. Three-dimensional magnetic resonance spectroscopic imaging of brain and prostate cancer. Neoplasia 2, 166-189 (2000).
90. 18F-labeled choline as an oncologic tracer for positron emission tomography: Initial findings in prostate cancer. Cancer Res. 61, 110-117 (2001).
91. Liu, D. et al. Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin. Br. J. Cancer 87, 783-789 (2002).
92. Chung, Y. L. et al. Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock protein 90 inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAG) in human colon cancer models. J. Natl Cancer Inst. 95, 1624-1633 (2003). MRS as a tool for detecting drug action.
93. Anthony, M. L., Zhao, M. & Brindle, K. M. Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells. J. Biol. Chem. 274, 19686-19692 (1999).
94. Dubray, B. et al. In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas. Radiother. Oncol. 46, 185-191 (1998).
95. Chang, J. et al. Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma. Cancer 89, 2145-2152 (2000).
96. Ellis, P. A. et al. Preoperative chemotherapy induces apoptosis in early breast cancer. Lancet 349, 849 (1997).
97. Meyn, R. E. et al. Heterogeneity in apoptosis development in irradiated murine tumours of different histologies. Int. J. Radiat. Biol. 64, 583-591 (1993).
98. Kettunen, M. I. & Brindle, K. M. Apoptosis detection using magnetic resonance imaging and spectroscopy. Prog. Nucl. Mag. Reson. Spectrosc. 47, 175-185. (2005).
99. Moffat, B. A. et al. Functional diffusion map: A noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc. Natl Acad. Sci. USA 102, 5524-5529 (2005). A clinically applicable and label-free MRI method for detecting early tumour responses to treatment.
100. Corsten, M. F., Hofstra, L., Narula, J. & Reutelingsperger, C. P. Counting heads in the war against cancer: defining the role of annexin A5 imaging in cancer treatment and surveillance. Cancer Res. 66, 1255-1260 (2006). A recent review describing the use of labelled annexin to detect cell death.
101. 99mTc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin. Cancer Res. 8, 2766-2774 (2002).
102. 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V. Eur. J. Nucl. Med. Mol. Imaging 34, 247-258 (2007).
103. Neves, A. A. et al. A paramagnetic nanoprobe to detect tumor cell death using magnetic resonance imaging. Nano Lett. 7, 1419-1423 (2007).
104. Petrovsky, A., Schellenberger, E., Josephson, L., Weissleder, R. & Bogdanov, A. Near-infrared fluorescent imaging of tumor apoptosis. Cancer Res. 63, 1936-1942 (2003).
105. Boersma, H. H. et al. Past, present, and future of annexin A5: from protein discovery to clinical applications. J. Nucl. Med. 46, 2035-2050 (2005).
106. Van Den Bossche, B. & de Wiele, C. V. Receptor imaging in oncology by means of nuclear medicine: Current status. J. Clin. Oncol. 22, 3593-3607 (2004).
107. Teunissen, J. J. M., Kwekkeboom, D. J. & Krenning, E. P. Staging and treatment of differentiated thyroid carcinoma with radiolabeled somatostatin analogs. Trends Endocrinol. Metab. 17, 19-25 (2006).
108. Linden, H. M. et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J. Clin. Oncol. 24, 2793-2799 (2006).
109. Dehdashti, F. et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur. J. Nuc. Med. Mol. Imaging 32, 344-350 (2005).
110. Orlova, A. et al. Tumor imaging using a picomolar affinity HER2 binding affibody molecule. Cancer Res. 66, 4339-4348 (2006).
111. Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249-257 (2000).
112. Tozer, G. M., Kanthou, C. & Baguley, B. C. Disrupting tumour blood vessels. Nature Rev. Cancer 5, 423-435 (2005).
113. Folkman, J. Angiogenesis. Annu. Rev. Med. 57, 1-18 (2006).
114. Miller, J. C., Pien, H. H., Sahani, D., Sorensen, A. G. & Thrall, J. H. Imaging angiogenesis: Applications and potential for drug development. J. Natl Cancer Inst. 97, 172-187 (2005).
115. Leach, M. O. et al. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br. J. Cancer 92, 1599-1610 (2005). A discussion of the methods for assessing response to anti-angiogenic and anti-vascular treatments using dynamic contrast agent-enhanced MRI.
116. McDonald, D. M. & Choyke, P. L. Imaging of angiogenesis: from microscope to clinic. Nature Med. 9, 713-725 (2003).
117. Morgan, B. et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies. J. Clin. Oncol. 21, 3955-3964 (2003).
118. Barrett, T., Kobayashi, H., Brechbiel, M. & Choyke, P. L. Macromolecular MRI contrast agents for imaging tumor angiogenesis. Eur. J. Radiol. 60, 353-366 (2006).
119. Abramovitch, R., Dafni, H., Smouha, E., Benjamin, L. E. & Neeman, M. In vivo prediction of vascular susceptibility to vascular endothelial growth factor withdrawal: magnetic resonance imaging of C6 rat glioma in nude mice. Cancer Res. 59, 5012-5016 (1999).
120. Beauregard, D. A., Hill, S. A., Chaplin, D. J. & Brindle, K. M. The susceptibility of tumors to the anti-vascular drug combretastatin A4 phosphate correlates with vascular permeability. Cancer Res. 61, 6811-6815 (2001).
121. 18F]galacto-RGD. PLOS Med. 2, 244-252 (2005).
122. Ljungkvist, A. S. E., Bussink, J., Kaanders, J. H. A. M. & Van der Kogel, A. J. Dynamics of tumor hypoxia measured with bioreductive hypoxic cell markers. Radiat. Res. 167, 127-145 (2007).
123. 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J. Nucl. Med. 46, 253-260 (2005).
124. 18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study. BMC Cancer 6, 51 (2006).
125. Czernin, J., Weber, W. A. & Herschman, H. R. Molecular imaging in the development of cancer therapeutics. Annu. Rev. Med. 57, 99-118 (2006).
126. 18F-FDG incorporation is enhanced by attenuation of p53 function in breast cancer cells in vitro. J. Nucl. Med. 47, 1525-1530 (2006).
127. Ho, C.-l., Chen, S., Yeung, D. W. C. & Cheng, T. K. C. Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma. J. Nucl. Med. 48, 902-909 (2007).
128. Segal, E. et al. Decoding global gene expression programs in liver cancer by noninvasive imaging. Nature Biotech. 25, 675-680 (2007). A fascinating study correlating defined imaging traits in CT scans with gene-expression profiles, raising the possibility that gene-expression programmes might be inferred from imaging studies.
129. Zhang, Y. Y., Brady, M. & Smith, S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans. Med. Imaging 20, 45-57 (2001).
130. Frese, K. K. & Tuveson, D. A. Maximizing mouse cancer models. Nature Rev. Cancer 7, 654-658 (2007). Realistic animal models of disease should assist the development of novel clinical imaging methods. This review describes the current state-of-the-art for these models.
131. Trepel, M., Arap, W. & Pasqualini, R. In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr. Opin. Chem. Biol. 6, 399-404 (2002).
132. Haubner, R. & Wester, H. R. Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies. Curr. Pharm. Design 10, 1439-1455 (2004).
133. Aina, O. H. et al. From combinatorial chemistry to cancer-targeting peptides. Mol. Pharm. 4, 631-651 (2007).
134. Serganova, I. & Blasberg, R. Reporter gene imaging: potential impact on therapy. Nucl. Med. Biol. 32, 763-780 (2005).
135. Tjuvajev, J. G. et al. Imaging adenoviral-mediated Herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res. 59, 5186-5193 (1999). An early example of a radionuclide-based gene reporter.
136. Genove, G., DeMarco, U., Xu, H. Y., Goins, W. F. & Ahrens, E. T. A new transgene reporter for in vivo magnetic resonance imaging. Nature Med. 11, 450-454 (2005).
137. Doubrovin, M. et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc. Natl Acad. Sci. USA 98, 9300-9305 (2001). An early example of the way a PET-based gene reporter can be used to image specific aspects of cell biology in vivo.
138. Zhou, J. Y. & van Zijl, P. C. M. Chemical exchange saturation transfer imaging and spectroscopy. Prog. Nucl. Mag. Res. Sp. 48, 109-136 (2006).
139. Aime, S. et al. Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J. Mag. Res. Imaging 16, 394-406 (2002).
140. Schröder, L., Lowery, T. J., Hilty, C., Wemmer, D. E. & Pines, A. Molecular imaging using a targeted magnetic resonance hyperpolarized biosensor. Science 314, 446-449 (2006).
141. Beekman, F. & van der Have, F. The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging. Eur. J. Nuc. Med. Mol. Imaging 34,151-161 (2007).
142. Salerno, M. et al. Hyperpolarized noble gas MR imaging of the lung: Potential clinical applications. Eur. J. Radiol. 40, 33-44 (2001).