Molecular imaging in the development of cancer therapeutics

Annual Review of Medicine

Volumn 57, Issue , 2006, Pages 99-118

  Czernin, Johannes ^a   Weber, Wolfgang A ^a   Herschman, Harvey R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Imaging probes; Positron emission tomography; Targeted drugs

Indexed keywords

ANGIOGENESIS; APOPTOSIS; CANCER RESEARCH; CANCER THERAPY; CELL HYPOXIA; CELL METABOLISM; CELL PROLIFERATION; GENE EXPRESSION; MOLECULAR IMAGING; PRIORITY JOURNAL; REPORTER GENE; REVIEW; SIGNAL TRANSDUCTION;

DRUG APPROVAL; FLUORODEOXYGLUCOSE F18; GENES, REPORTER; HUMANS; MOLECULAR PROBE TECHNIQUES; NEOPLASMS; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS;

EID: 32944479631     PISSN: 00664219     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.med.57.080904.190431     Document Type: Review

References (136)

1. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70
2. Moertel C, Hanley J. 1976. The effect of measuring error on the results of therapeutic trials in advanced cancer. Cancer 38:388-94
3. Miller A, Hoogstraten B, Staquet M, et al. 1981. Reporting results of cancer treatment. Cancer 47:207-14
4. Therasse P, Arbuck SG, Eisenhauer EA, et al. 2000. New guidelines to evaluate the response to treatment in solid tumors. J. Natl. Cancer Inst. 92:205-16
5. Shepherd F, Pereira J, Ciuleanu T, et al. 2004. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. J. Clin. Oncol. 22:A-7022
6. Phelps M. 2000. Positron emission tomography provides molecular imaging of biological processes. PNAS 97:9226-33
7. Herschman HR. 2003. Molecular imaging: looking at problems, seeing solutions. Science 302:605-8
8. Massoud T, Gambhir S. 2003. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 17:545-80
9. Weissleder RVN. 2003. Shedding light onto live molecular targets. Nat. Med. 9:123-28
10. Raghunand N, Gatenby RA, Gillies RJ. 2003. Microenvironmental and cellular consequences of altered blood flow in tumours. Br. J. Radiol. 76:811-22
11. Leach MO, Brindle KM, Evelhoch JL, et al. 2003. Assessment of antiangiogenic and antivascular therapeutics using MRI: recommendations for appropriate methodology for clinical trials. Br. J. Radiol. 76:S87-91
12. Kiessling F, Greschus S, Lichy M, et al. 2004. Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis. Nat. Med. 10:1133-38
13. Lam K. 1997. Application of combinatorial library methods in cancer research and drug discovery. Anticancer Drug Des. 12:145-67
14. Burbaum J, Ohlmeyer M, Reader J, et al. 1995. A paradigm for drug discovery employing encoded combinatorial libraries. PNAS 92:6027-31
15. Burbaum J, Sigal N. 1997. New technologies for high-throughput screening. Curr. Opin. Chem. Biol. 1:72-78
16. Lesko LJ, Rowland M, Peck CC, et al. 2000. Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans. Pharm. Res. 17:1335-44
17. Knowles J, Gromo G. 2003. Target selection in drug discovery. Nat. Rev. Drug Discov. 2:63-69
18. Lindsay M. 2003. Target discovery. Nat Rev. Drug Discov. 2:831-38
19. DiMasi JA, Hansen RW, Grabowski HG. 2003. The price of innovation: new estimates of drug development costs. J. Health Econ. 22:151-85
20. Hirst G, Balmain A. 2004. Forty years of cancer modelling in the mouse. Eur. J. Cancer 40:1974-80
21. Graham DJ, Campen D, Hui R, et al. 2005. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 365:475-81
22. Nussmeier NA, Whelton AA, Brown MT, et al. 2005. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N. Engl. J. Med. 352:1081-91
23. Bresalier RS, Sandler RS, Quan H, et al. 2005. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N. Engl. J. Med. 352:1092-102
24. DiMasi J. 2002. The value of improving the productivity of the drug development process: faster times and better decisions. Pharmacoeconomics 20:1-10
25. Dickson M, Gagnon J. 2004. Key factors in the rising cost of new drug discovery and development. Nat. Rev. Drug Discov. 3:417-29
26. Phelps M, Hoffmann E, Mullani N, et al. 1975. Application of annihilation coincidence detection to transaxial reconstruction tomography. J. Nucl. Med. 16:210-24
27. Cherry S, Gambhir S. 2001. Use of positron emission tomography in animal research. ILAR J. 42:219-32
28. Chatziioannou A, Tai Y, Doshi N, et al. 2001. Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging. Phys. Med. Biol. 46:2899-910
29. Chatziioannou A, Cherry S, Shao Y, et al. 1999. Performance evaluation of microPET: a high resolution lutetium oxyorthosilicate PET scanner for animal imaging. J. Nucl. Med. 40:1164-75
30. Dahlbom M, Hoffman E, Hoh C, et al. 1992. Whole-body positron emission tomography: Part I. Methods and performance characteristics. J. Nucl. Med. 33:1191-99
31. Hoekstra CJ, Paglianiti I, Hoekstra OS, et al. 2000. Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-glucose and positron emission tomography: an overview of different analytical methods. Eur. J. Nucl. Med. Mol. Imag. 27:731-43
32. Buxton D, Nienaber C, Luxen A, et al. 1989. Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C] acetate and dynamic positron emission tomography. Circulation 79:134-42
33. Muzi M, Mankoff DA, Grierson JR, et al. 2005. Kinetic modeling of 3′-deoxy-3′-fluorothymidine in somatic tumors: mathematical studies. J. Nucl. Med. 46:371-80
34. Muzi M, Vesselle H, Grierson JR, et al. 2005. Kinetic analysis of 3′-deoxy-3′-fluorothymidine PET studies: validation studies in patients with lung cancer. J. Nucl. Med. 46:274-82
35. Paulus M, Gleason S, Kennel S, et al. 2000. High resolution X-ray computed tomography: an emerging tool for small animal cancer research. Neoplasia 2:62-70
36. von Schulthess GK. 2004. Positron emission tomography versus positron emission tomography/computed tomography: from "unclear" to "new-clear" medicine. Mol. Imag. Biol. 6:183-87
37. Ntziachristos V, Tung CH, Bremer C, et al. 2002. Fluorescence molecular tomography resolves protease activity in vivo. Nat. Med. 8:757-60
38. Herschman HR. 2004. Noninvasive imaging of reporter gene expression in living subjects. Adv. Cancer Res. 92:29-80
39. Lynch TJ, Bell DW, Sordella R, et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:2129-39
40. Paez J, Janne P, Lee J, et al. 2004. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497-500
41. Pao W, Miller V, Politi K, et al. 2005. Acquired resistance of lung adenocarcinomas to gefitinib is associated with a second mutation in the EGFR kinase domain. PLOS Medicine 2:1-11
42. Stephens P, Hunter C, Bignell G, et al. 2004. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431:525-26
43. Sordella R, Bell DW, Haber DA, et al. 2004. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163-67
44. Marx J. 2004. Why a new cancer drug works well, in some patients. Science 304:658a-59a
45. Arao T, Fukumoto H, Takeda M, et al. 2004. Small inframe deletion in the epidermal growth factor receptor as a target for ZD6474. Cancer Res. 64:9101-4
46. Doubrovin M, Ponomarev V, Beresten T, et al. 2001. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. PNAS 98:9300-5
47. Wen B, Burgman P, Zanzonico P, et al. 2004. A preclinical model for noninvasive imaging of hypoxia-induced gene expression; comparison with an exogenous marker of tumor hypoxia. Eur. J. Nucl. Med. Mol. Imag. 31:1530-38
48. Iyer M, Wu L, Carey M, et al. 2001. Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. PNAS 98:14595-600
49. Gatenby R, Gillies R. 2004. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4:891-99
50. Smith T. 1999. Facultative glucose transporter expression in human cancer tissue. Br. J. Biomed. Sci. 4:285-92
51. Smith TAD. 2001. The rate-limiting step for tumor [18F]fluoro-2-deoxy-D- glucose (FDG) incorporation. Nucl. Med. Biol. 28:1-4
52. Vander Heiden MG, Plas DR, Rathmell JC, et al. 2001. Growth factors can influence cell growth and survival through effects on glucose metabolism. Mol. Cell Biol. 21:5899-912
53. Majumder PK, Febbo PG, Bikoff R, et al. 2004. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat. Med. 10:594-601
54. Elstrom RL, Bauer DE, Buzzai M, et al. 2004. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64:3892-99
55. Stroobants S, Goeminne J, Seegers M, et al. 2003. ISFDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur. J. Cancer 39:2012-20
56. Weber WA, Petersen V, Schmidt B, et al. 2003. Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J. Clin. Oncol. 21:2651-57
57. Weber W, Ott K, Becker K, et al. 2001. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin. Oncol. 19:3058-65
58. Spaepen K, Stroobants S, Dupont P, et al. 2001. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: Is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J. Clin. Oncol. 19:414-19
59. Filmont JE, Czernin J, Yap C, et al. 2003. Value of F-18 fluorodeoxy glucose positron emission tomography for predicting the clinical outcome of patients with aggres sive lymphoma prior to and after autologous stem-cell transplantation. Chest 124:608-13
60. Schelling M, Avril N, Nahrig J, et al. 2000. Positron emission tomography using [(18)F] fluorodeoxy glucose for monitoring primary chemotherapy in breast cancer. J. Clin. Oncol. 18:1689-95
61. Higashi K, Clavo AC, Wahl RL. 1993. In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J. Nucl. Med. 34:773-79
62. Senekowitsch-Schmidtke R, Matzen K, Truckenbrodt R, et al. 1998. Tumor cell spheroids as a model for evaluation of metabolic changes after irradiation. J. Nucl. Med. 39:1762-68
63. Haberkorn U, Bellemann ME, Altmann A, et al. 1997. PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine. J. Nucl. Med. 38:1215-21
64. Jager PL, Vaalburg W, Pruim J, et al. 2001. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J. Nucl. Med. 42:432-45
65. Mastroberardino L, Spindler B, Pfeiffer R, et al. 1998. Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature 395:288-91
66. Bustany P, Chatel M, Derlon J, et al. 1986. Brain tumor protein synthesis and histological grades: a study by positron emission tomography (PET) with C11-L-methionine. J. Neurooncol. 3:397-404
67. Stout DB, Huang SC, Melega WP, et al. 1998. Effects of large neutral amino acid concentrations on 6-[F-18]fluoro-L-DOPA kinetics. J. Cereb. Blood Flow Metab. 18:43-51
68. Becherer A, Karanikas G, Szabo M, et al. 2003. Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine. Eur. J. Nucl. Med. Mol. Imag. 30:1561-67
69. Wester H, Herz M, Weber W, et al. 1999. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J. Nucl. Med. 40:205-12
70. Inoue T, Tomiyoshi K, Higuichi T, et al. 1998. Biodistribution studies on L-3-fluorine-18 fluoro-alpha-methyl-tyrosine: a potential tumor detecting agent. J. Nucl. Med. 39:663-67
71. Edinger AL, Thompson CB. 2002. Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol. Biol. Cell 13:2276-88
72. Baldwin JE, Krebs H. 1981. The evolution of metabolic cycles. Nature 291:381-82
73. Seltzer MA, Jahan SA, Dahlbom M, et al. 2003. Combined metabolic imaging using C-11 acetate and FDG PET for the evaluation of patients with suspected recurrent prostate cancer. J. Nucl. Med. 44:132P (Abstr.)
74. Shreve P, Chiao PC, Humes HD, et al. 1995. Carbon-11-acetate PET imaging in renal disease. J. Nucl. Med. 36:1595-601
75. Van de Sande T, De Schrijver E, Heyns W, et al. 2002. Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Res. 62:642-46
76. Hara T, Kosaka N, Suzuki T, et al. 2003. Uptake rates of 18F-fluorodeoxyglucose and HC-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest 124:893-901
77. DeGrado TR, Baldwin SW, Wang S, et al. 2001. Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J. Nucl. Med. 42:1805-14
78. Hara T, Kosaka N, Kishi H. 2002. Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J. Nucl. Med. 43:187-99
79. Ramirez de Molina A, Penalva V, Lucas L, et al. 2002. Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K. Oncogene 21:937-46
80. Ramirez de Molina A, Rodriguez-Gonzalez A, Penalva V, et al. 2001. Inhibition of ChoK is an efficient antitumor strategy for Harvey-, Kirsten-, and N-ras-transformed cells. Biochem. Biophys. Res. Commun. 285:873-79
81. Liu D, Hutchinson OC, Osman S, et al. 2002. Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin. Br. J. Cancer 87:783-89
82. Griffiths M, Beaumont N, Yao SY, et al. 1997. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat. Med. 3:89-93
83. Shields AF, Grierson JR, Dohmen BM, et al. 1998. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat. Med. 4:1334-36
84. Shields AF, Mankoff DA, Link JM, et al. 1998. Carbon-11-thymidine and FDG to measure therapy response. J. Nucl. Med. 39:1757-62
85. Schwartz JL, Tamura Y, Jordan R, et al. 2003. Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine and thymidine analogs. J. Nucl. Med. 44:2027-32
86. Waldherr C, Mellinghoff IK, Tran C, et al. 2005. Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3′-deoxy-3′-18F-fluorothymidine PET. J. Nucl. Med. 46:114-20
87. Rasey JS, Grierson JR, Wiens LW, et al. 2002. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J. Nucl. Med. 43:1210-17
88. Wagner M, Seitz U, Buck A, et al. 2003. 3′-[18F]fluoro-3′- deoxythymidine ([18F]-FLT) as positron emission tomography tracer for imaging proliferation in a murine B-cell lymphoma model and in the human disease. Cancer Res. 63:2681-87
89. Visvikis D, Francis D, Mulligan R, et al. 2003. Comparison of methodologies for the in vivo assessment of (18)FLT utilisation in colorectal cancer. Eur. J. Nucl. Med. Mol. Imag. 31(2):169-78
90. Buck AK, Schirrmeister H, Hetzel M, et al. 2002. 3-deoxy-3-[(18)F] fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res. 62:3331-34
91. Vesselle H, Grierson J, Muzi M, et al. 2002. In vivo validation of 3′deoxy-3′-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin. Cancer Res. 8:3315-23
92. Barthel H, Cleij MC, Collingridge DR, et al. 2003. 3′-deoxy- 3′-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res. 63:3791-98
93. Pio BS, Park CK, Satyamurthy N, et al. 2003. PET with fluoro-L-thymidine allows early prediction of breast cancer response to chemotherapy. J. Nucl. Med. 44:76P-77P
94. Cohen S, Carpenter G, King LJ. 1980. Epidermal growth factor receptor kinase interaction: co-purification of receptor and epidermal growth factor enhanced phosphorylation activity. J. Biol. Chem. 255:4834-42
95. Seimbille Y, Azarian V, Czernin J, et al. 2004. A new series of F-18 labeled anilinoquinazoline derivatives for PET imaging of tyrosine kinase receptors. J. Nucl. Med. 5(Suppl.):448P
96. Waldherr C, Satyamurthy N, Toyokuni T, et al. 2003. Evaluation of N-[4-(3′-F-18 fluoroethylphenyl)amino-6-quinazolinyl]acrylamide (F-18 FEQA), a labeled tyrosine kinase inhibitor, for imaging epidermal growth factor receptor density. J. Nucl. Med. 44:372P (Abstr.)
97. Shaul M, Abourbeh G, Jacobson O, et al. 2004. Novel iodine-124 labeled EGFR inhibitors as potential PET agents for molecular imaging in cancer. Bioorg. Med. Chem. 12:3421-29
98. Molls M, Stadler P, Becker A, et al. 1998. Relevance of oxygen in radiation oncology: mechanisms of action, correlation to low hemoglobin levels. J. Strahlenther. Onkol. 174:13-16
99. Lehtiö K, Eskola O, Viljanen T, et al. 2004. Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 59:971-82
100. Carmeliet P, Jain R. 2000. Angiogenesis in cancer and other diseases. Nature 407:249-57
101. Nunn A, Linder K, Srauss H. 1995. Niroimidazoles and imaging hypoxia. Eur. J. Nucl. Med. 22:265-80
102. Chapman J. 1979. Hypoxic sensitizers: implications for radiation therapy. N. Engl. J. Med. 301:1429-32
103. Koh W, Bergman K, Rasey JS. 1995. Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. Int. J. Radiat. Oncol. Biol. Phys. 33:391-98
104. Dubois L, Landuyt W, Haustermans K, et al. 2004. Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry. Br. J. Cancer 91:1947-54
105. Rajendran JG, Mankoff DA, O'Sullivan F, et al. 2004. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin. Cancer Res. 10:2245-52
106. Henk J, Smith C. 1977. Radiotherapy and hyperbaric oxygen in head and neck cancer. Interim report of second clinical trial. Lancet 2:104-5
107. Chao KSC, Bosch WR, Mutic S, et al. 2001. A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy. Int. J. Rad. Oncol. Biol. Phys. 49:1171-82
108. Dehdashti F, Mintun MA, Lewis JS, et al. 2003. In vivo assessment of tumor hypoxia in lung cancer with Cu-ATSM. Eur. J. Nucl. Med. Mol. Imag. 30:844-50
109. Leung D, Cachianes G, Kuang W, et al. 1989. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306-9
110. Davis D, McConkey D, Abbruzzese J, et al. 2003. Surrogate markers in antiangiogenesis clinical trials. Br. J. Cancer 89:8-14
111. Yang JC, Haworth L, Sherry RM, et al. 2003. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med. 349:427-34
112. Rehman S, Jayson GC. 2005. Molecular imaging of antiangiogenic agents. Oncologist 10:92-103
113. Miller JC, Pien HH, Sahani D, et al. 2005. Imaging angiogenesis: applications and potential for drug development. J. Natl. Cancer Inst. 97:172-87
114. Bremer C, Mustafa M, Bogdanov A Jr, et al. 2003. Steady-state blood volume measurements in experimental tumors with different angiogenic burdens-a study in mice. Radiology 226:214-20
115. McDonald DM, Choyke PL. 2003. Imaging of angiogenesis: from microscope to clinic. 9:713-25
116. Wilson CB, Lammertsma AA, McKenzie CG, et al. 1992. Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method. Cancer Res. 52:1592-97
117. Collingridge DR, Carroll VA, Glaser M, et al. 2002. The development of [124I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Res. 62:5912-19
118. Haubner R, Wester HJ, Reuning U, et al. 1999. Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. J. Nucl. Med. 40:1061-71
119. Haubner R, Weber WA, Beer AJ, et al. 2005. Noninvasive visualization of the activated alpha(v)beta3 integrin in cancer patients by positron emission tomography and [(18)F]galacto-RGD. PLOS Med. In press
120. Haubner R, Kuhnast B, Mang C, et al. 2004. [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. Bioconjug. Chem. 15:61-69
121. Santimaria M, Moscatelli G, Viale GL, et al. 2003. Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. Clin. Cancer Res. 9:571-79
122. Stupack DG, Cheresh DA. 2004. Integrins and angiogenesis. Curr. Top. Dev. Biol. 64:207-38
123. Ruoslahti E. 2003. The RGD story: a personal account. Matrix Biol. 22:459-65
124. Dechantsreiter MA, Planker E, Matha B, et al. 1999. N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J. Med. Chem. 42:3033-40
125. van Hagen PM, Breeman WA, Bernard HF, et al. 2000. Evaluation of a radio-labelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy. Int. J. Cancer 90:186-98
126. Haubner R, Wester H-J, Weber WA, et al. 2001. Noninvasive imaging of αvβ3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 61:1781-85
127. Janssen M, Oyen WJ, Massuger LF, et al. 2002. Comparison of a monomeric and dimeric radiolabeled RGD-peptide for tumor targeting. Cancer Biother. Radiopharm. 17:641-46
128. Janssen ML, Oyen WJ, Dijkgraaf I, et al. 2002. Tumor targeting with radiolabeled alpha(v)beta(3) integrin binding peptides in a nude mouse model. Cancer Res. 62:6146-51
129. Chen X, Conti PS, Moats RA. 2004. In vivo near-infrared fluorescence imaging of integrin alphavbeta3 in brain tumor xenografts. Cancer Res. 64:8009-14
130. Sipkins DA, Cheresh DA, Kazemi MR, et al. 1998. Detection of tumor angiogenesis in vivo by [alpha]v[beta]3-targeted magnetic resonance imaging. 4:623-26
131. Ken J, Wyllie A, Currie A. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-57
132. Blankenberg FG, Katsikis PD, Tait JF, et al. 1998. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. PNAS 95:6349-54
133. Brindle KM. 2003. Molecular imaging using magnetic resonance: new tools for the development of tumour therapy. Br. J. Radiol. 76:8111-17
134. Schellenberger E, Bogdanov A, Högemann H, et al. 2002. Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Mol. Imag. 1:102-7
135. Bergstrom M, Grahnann A, Langstrom B. 2003. Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development. Eur. J. Clin. Pharmacol. 59:357-66
136. Lappin G, Garner RC. 2003. Big physics, small doses: the use of AMS and PET in human microdosing of development drugs. Nat. Rev. Drug Discov. 2:233-40