Angiogenesis

, 11:321 | Cite as

Circulating and imaging markers for angiogenesis

  • Arvind P. Pathak
  • Warren E. Hochfeld
  • Simon L. Goodman
  • Michael S. Pepper
Review Paper

Abstract

Abundant preclinical and indirect clinical data have for several decades convincingly supported the notion that anti-angiogenesis is an effective strategy for the inhibition of tumor growth. The recent success achieved in patients with metastatic colon carcinoma using a neutralizing antibody directed against vascular endothelial growth factor (VEGF) has translated preclinical optimism into a clinical reality.With this transformation in the field of angiogenesis has come a need for reliable surrogate markers. A surrogate marker by definition serves as a substitute for the underlying process in question, and in the case of angiogenesis, microvessel density (usually in so-called “hot-spots”) has until now been the most widely used parameter. However, this parameter is more akin to a static “snap-shot” and does not lend itself either to the dynamic in situ assessment of the status of the tumor microvasculature or to the molecular factors that regulate its growth and involution. This has led to an acute need for developing circulating and imaging markers of angiogenesis that can be monitored in vivo at repeated intervals in large number of patients with a variety of tumors in a non-invasive manner. Such markers of angiogenesis are the subject of this review.

Keywords

Circulating Angiogenesis Imaging Marker Surrogate 

Notes

Acknowledgment

Supported by NIH P50CA103175 Career Development Award (APP).

References

  1. 1.
    Angiogenesis inhibitors in clinical trials 2007 Available from: http://www.cancer.gov/clinicaltrials/developments/anti-angio-table
  2. 2.
    Madhusudan S, Harris AL (2002) Drug inhibition of angiogenesis. Curr Opin Pharmacol 2(4):403–414. doi: 10.1016/S1471-4892(02)00184-4 PubMedGoogle Scholar
  3. 3.
    Park JW, Kerbel RS, Kelloff GJ, Barrett JC, Chabner BA, Parkinson DR, Peck J, Ruddon RW, Sigman CC, Slamon DJ (2004) Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin Cancer Res 10(11):3885–3896. doi: 10.1158/1078-0432.CCR-03-0785 PubMedGoogle Scholar
  4. 4.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342. doi: 10.1056/NEJMoa032691 PubMedGoogle Scholar
  5. 5.
    Crew JP (1999) Vascular endothelial growth factor: an important angiogenic mediator in bladder cancer. Eur Urol 35(1):2–8. doi: 10.1159/000019811 PubMedGoogle Scholar
  6. 6.
    Schneider M, Tjwa M, Carmeliet P (2005) A surrogate marker to monitor angiogenesis at last. Cancer Cell 7(1):3–4. doi: 10.1016/j.ccr.2004.12.014 PubMedGoogle Scholar
  7. 7.
    Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989. doi: 10.1038/nm0901-987 PubMedGoogle Scholar
  8. 8.
    Fox SB, Harris AL (2004) Histological quantification of tumour angiogenesis. APMIS 112(7–8):413–430. doi: 10.1111/j.1600-0463.2004.apm11207-0803.x PubMedGoogle Scholar
  9. 9.
    Holash P, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998. doi: 10.1126/science.284.5422.1994 PubMedGoogle Scholar
  10. 10.
    Maniotis AJ, Folgberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJC (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155(3):739–752PubMedGoogle Scholar
  11. 11.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8PubMedGoogle Scholar
  12. 12.
    Sarbia M, Bittinger F, Porschen R, Dutkowski P, Willers R, Gabbert HE (1996) Tumor vascularization and prognosis in squamous cell carcinomas of the esophagus. Anticancer Res 15:2117–2122Google Scholar
  13. 13.
    Bossi P, Viale G, Lee AKC, Alfano RM, Coggi G, Bosari S (1995) Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations. Cancer Res 55:5049–5053PubMedGoogle Scholar
  14. 14.
    Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9(4):539–549PubMedGoogle Scholar
  15. 15.
    Steinberg F, Rohrborn HJ, Otto T, Scheufler KM, Streffer C (1997) NIR reflection measurements of hemoglobin and cytochrome aa3 in healthy tissues and tumors. Correlations to oxygen consumption: preclinical and clinical data. Adv Exp Med Biol 428:69–77PubMedGoogle Scholar
  16. 16.
    Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Natl Cancer Inst 94(12):883–893PubMedGoogle Scholar
  17. 17.
    Ellis LM, Walker RA, Gasparini G (1998) Current controversies in cancer: is determination of angiogenic activity in human clinically useful? Eur J Cancer 34(5):609–618. doi: 10.1016/S0959-8049(97)10040-5 PubMedGoogle Scholar
  18. 18.
    Ruegg C, Meuwly JY, Driscoll R, Werffeli P, Zaman K, Stupp R (2003) The quest for surrogate markers of angiogenesis: a paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials. Curr Mol Med 3(8):673–691. doi: 10.2174/1566524033479410 PubMedGoogle Scholar
  19. 19.
    Poptani H, Puumalainen AM, Grohn OI, Loimas S, Kainulainen R, Yla-Herttuala S, Kauppinen RA (1998) Monitoring thymide kinase and gancicliovir-induced changes in rat malignant glioma in vivo by NMR. Cancer Gene Ther 5(2):101–109PubMedGoogle Scholar
  20. 20.
    Lindner DJ, Borden EC (1997) Effects of tamoxifen and interferon-beta on tumor-induced angiogenesis. Int J Cancer 71(3):456–461. doi:10.1002/(SICI)1097-0215(19970502)71:3<456::AID-IJC25>3.0.CO;2-CPubMedGoogle Scholar
  21. 21.
    McDonald DM, Choyke PL (2003) Imaging of angiogenesis: from microscope to clinic. Nat Med 9(6):713–725. doi: 10.1038/nm0603-713 PubMedGoogle Scholar
  22. 22.
    Pathak AP, Gimi B, Glunde K, Ackerstaf E, Artemov D, Bhujwalla ZM (2004) Molecular and functional imaging of cancer: advances in MRI and MRS. Methods Enzymol 386:3–60PubMedGoogle Scholar
  23. 23.
    Pathak AP, Artemov D, Ward BD, Jackson DG, Neeman M, Bhujwalla ZM (2005) Characterizing extravascular fluid transport of macromolecules in the tumor interstitium by magnetic resonance imaging. Cancer Res 65(4):1425–1432. doi: 10.1158/0008-5472.CAN-04-3682 PubMedGoogle Scholar
  24. 24.
    Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5(12):1359–1364. doi: 10.1038/70928 PubMedGoogle Scholar
  25. 25.
    Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732. doi: 10.1038/nrc1187 PubMedGoogle Scholar
  26. 26.
    Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2(10):737–744. doi: 10.1038/35036374 PubMedGoogle Scholar
  27. 27.
    De Paola F, Granato AM, Scarpi E, Monti F, Medri L, Bianchi S, Amadori D, Volpi A (2002) Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer. Int J Cancer 98(2):228–233. doi: 10.1002/ijc.10118 PubMedGoogle Scholar
  28. 28.
    MacConmara M, O’Hanlon DM, Kiely MJ, Connolly Y, Jeffers M, Keane FB (2002) An evaluation of the prognostic significance of vascular endothelial growth factor in node positive primary breast carcinoma. Int J Oncol 20(4):717–721PubMedGoogle Scholar
  29. 29.
    Poon RT, Fan ST, Wong J (2001) Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19(4):1207–1225PubMedGoogle Scholar
  30. 30.
    Drevs J, Laus C, Medinger M, Schmidt-Gersbach C, Unger C (2002) Antiangiogenesis: current clinical data and future perspectives. Onkologie 25(6):520–527. doi: 10.1159/000068622 PubMedGoogle Scholar
  31. 31.
    Kleespies A, Guba M, Jauch KW, Bruns CJ (2004) Vascular endothelial growth factor in esophageal cancer. J Surg Oncol 87(2):95–104. doi: 10.1002/jso.20070 PubMedGoogle Scholar
  32. 32.
    Fuhrmann-Benzakein E, Ma MN, Rubbia-Brandt L, Mentha G, Ruefenacht D, Sappino AP, Pepper MS (2000) Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int J Cancer 85(1):40–45. doi:10.1002/(SICI)1097-0215(20000101)85:1<40::AID-IJC7>3.0.CO;2-LPubMedGoogle Scholar
  33. 33.
    Gasparini G (2001) Clinical significance of determination of surrogate markers of angiogenesis in breast cancer. Crit Rev Oncol Hematol 37(2):97–114. doi: 10.1016/S1040-8428(00)00105-0 PubMedGoogle Scholar
  34. 34.
    Kumar H, Heer K, Greenman J, Kerin MJ, Monson JR (2002) Soluble FLT-1 is detectable in the sera of colorectal and breast cancer patients. Anticancer Res 22(3):1877–1880PubMedGoogle Scholar
  35. 35.
    Ebos JM, Bocci G, Man S, Thorpe PE, Hicklin DJ, Zhou D, Jia X, Kerbel RS (2004) A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res 2(6):315–326PubMedGoogle Scholar
  36. 36.
    Bocci G, Man S, Green SK, Francia G, Ebos JM, du Manoir JM, Weinerman A, Emmenegger U, Ma L, Thorpe P, Davidoff A, Huber J, Hicklin DJ, Kerbel RS (2004) Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies. Cancer Res 64(18):6616–6625. doi: 10.1158/0008-5472.CAN-04-0401 PubMedGoogle Scholar
  37. 37.
    Drevs J (2003) Soluble markers for the detection of hypoxia under antiangiogenic treatment. Anticancer Res 23(2A):1159–1161PubMedGoogle Scholar
  38. 38.
    Byrne GJ, Bundred NJ (2000) Surrogate markers of tumoral angiogenesis. Int J Biol Markers 15(4):334–339PubMedGoogle Scholar
  39. 39.
    Bocci G, Francia G, Man S, Lawler J, Kerbel RS (2003) Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci USA 100(22):12917–12922. doi: 10.1073/pnas.2135406100 PubMedGoogle Scholar
  40. 40.
    Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967. doi: 10.1126/science.275.5302.964 PubMedGoogle Scholar
  41. 41.
    Mancuso P, Burlini A, Pruneri G, Goldhirsch A, Martinelli G, Bertolini F (2001) Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 97(11):3658–3661. doi: 10.1182/blood.V97.11.3658 PubMedGoogle Scholar
  42. 42.
    Beaudry P, Force J, Naumov GN, Wang A, Baker CH, Ryan A, Soker S, Johnson BE, Folkman J, Heymach JV (2005) Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity. Clin Cancer Res 11(9):3514–3522. doi: 10.1158/1078-0432.CCR-04-2271 PubMedGoogle Scholar
  43. 43.
    Monestiroli S, Mancuso P, Burlini A, Pruneri G, Dell’Agnola C, Gobbi A, Martinelli G, Bertolini F (2001) Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma. Cancer Res 61(11):4341–4344PubMedGoogle Scholar
  44. 44.
    Shaked Y, Bertolini F, Man S, Rogers MS, Cervi D, Foutz T, Rawn K, Voskas D, Dumont DJ, Ben-David Y, Lawler J, Henkin J, Huber J, Hicklin DJ, D’Amato RJ, Kerbel RS (2005) Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7(1):101–111PubMedGoogle Scholar
  45. 45.
    Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10(2):145–147. doi: 10.1038/nm988 PubMedGoogle Scholar
  46. 46.
    Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, Sahani DV, Kalva SP, Cohen KS, Scadden DT, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Shellito PC, Mino-Kenudson M, Lauwers GY (2005) Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 23(31):8136–8139. doi: 10.1200/JCO.2005.02.5635 PubMedGoogle Scholar
  47. 47.
    Beerepoot LV, Mehra N, Vermaat JS, Zonnenberg BA, Gebbink MF, Voest EE (2004) Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol 15(1):139–145. doi: 10.1093/annonc/mdh017 PubMedGoogle Scholar
  48. 48.
    Elshal MF, Khan SS, Takahashi Y, Solomon MA, McCoy JP Jr (2005) CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood. Blood 106(8):2923–2924. doi: 10.1182/blood-2005-06-2307 PubMedGoogle Scholar
  49. 49.
    Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, Pollok K, Ferkowicz MJ, Gilley D, Yoder MC (2004) Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 104(9):2752–2760. doi: 10.1182/blood-2004-04-1396 PubMedGoogle Scholar
  50. 50.
    St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (2000) Genes expressed in human tumor endothelium. Science 289(5482):1197–1202. doi: 10.1126/science.289.5482.1197 PubMedGoogle Scholar
  51. 51.
    Filshie RJ, Zannettino AC, Makrynikola V, Gronthos S, Henniker AJ, Bendall LJ, Gottlieb DJ, Simmons PJ, Bradstock KF (1998) MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies. Leukemia 12(3):414–421. doi: 10.1038/sj.leu.2400922 PubMedGoogle Scholar
  52. 52.
    Khan SS, Solomon MA, McCoy JP Jr (2005) Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 64(1):1–8. doi: 10.1002/cyto.b.20040 PubMedGoogle Scholar
  53. 53.
    Schon M, Kahne T, Gollnick H, Schon MP (2005) Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM). J Invest Dermatol 125(2):353–363PubMedGoogle Scholar
  54. 54.
    Stroun M, Anker P, Lyautey J, Lederrey C, Maurice PA (1987) Isolation and characterization of DNA from the plasma of cancer patients. Eur J Cancer Clin Oncol 23(6):707–712. doi: 10.1016/0277-5379(87)90266-5 PubMedGoogle Scholar
  55. 55.
    Taback B, Fujiwara Y, Wang HJ, Foshag LJ, Morton DL, Hoon DS (2001) Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients. Cancer Res 61(15):5723–5726PubMedGoogle Scholar
  56. 56.
    Taback B, Hoon DS (2004) Circulating nucleic acids and proteomics of plasma/serum: clinical utility. Ann N Y Acad Sci 1022:1–8. doi: 10.1196/annals.1318.002 PubMedGoogle Scholar
  57. 57.
    Taback B, O’Day SJ, Hoon DS (2004) Quantification of circulating DNA in the plasma and serum of cancer patients. Ann N Y Acad Sci 1022:17–24. doi: 10.1196/annals.1318.004 PubMedGoogle Scholar
  58. 58.
    Swisher EM, Wollan M, Mahtani SM, Willner JB, Garcia R, Goff BA, King MC (2005) Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am J Obstet Gynecol 193(3 Pt 1):662–667. doi: 10.1016/j.ajog.2005.01.054 PubMedGoogle Scholar
  59. 59.
    Vlahou A, Schorge JO, Gregory BW, Coleman RL (2003) Diagnosis of ovarian cancer using decision tree classification of mass spectral data. J Biomed Biotechnol 5:308–314. doi: 10.1155/S1110724303210032 Google Scholar
  60. 60.
    Xiao X, Zhao X, Liu J, Guo F, Liu D, He D (2004) Discovery of laryngeal carcinoma by serum proteomic pattern analysis. Sci China C Life Sci 47(3):219–223. doi: 10.1360/03yc0105 PubMedGoogle Scholar
  61. 61.
    Petricoin EF, Liotta LA (2004) Proteomic approaches in cancer risk and response assessment. Trends Mol Med 10(2):59–64. doi: 10.1016/j.molmed.2003.12.006 PubMedGoogle Scholar
  62. 62.
    Wadsworth JT, Somers KD, Cazares LH, Malik G, Adam BL, Stack BC Jr, Wright GL Jr, Semmes OJ (2004) Serum protein profiles to identify head and neck cancer. Clin Cancer Res 10(5):1625–1632. doi: 10.1158/1078-0432.CCR-0297-3 PubMedGoogle Scholar
  63. 63.
    Steel LF, Shumpert D, Trotter M, Seeholzer SH, Evans AA, London WT, Dwek R, Block TM (2003) A strategy for the comparative analysis of serum proteomes for the discovery of biomarkers for hepatocellular carcinoma. Proteomics 3(5):601–609. doi: 10.1002/pmic.200300399 PubMedGoogle Scholar
  64. 64.
    Poon TC, Yip TT, Chan AT, Yip C, Yip V, Mok TS, Lee CC, Leung TW, Ho SK, Johnson PJ (2003) Comprehensive proteomic profiling identifies serum proteomic signatures for detection of hepatocellular carcinoma and its subtypes. Clin Chem 49(5):752–760. doi: 10.1373/49.5.752 PubMedGoogle Scholar
  65. 65.
    Hood BL, Lucas DA, Kim G, Chan KC, Blonder J, Issaq HJ, Veenstra TD, Conrads TP, Pollet I, Karsan A (2005) Quantitative analysis of the low molecular weight serum proteome using 18O stable isotope labeling in a lung tumor xenograft mouse model. J Am Soc Mass Spectrom 16(8):1221–1230. doi: 10.1016/j.jasms.2005.02.005 PubMedGoogle Scholar
  66. 66.
    Koomen JM, Li D, Xiao LC, Liu TC, Coombes KR, Abbruzzese J, Kobayashi R (2005) Direct tandem mass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery. J Proteome Res 4(3):972–981. doi: 10.1021/pr050046x PubMedGoogle Scholar
  67. 67.
    Juan HF, Chen JH, Hsu WT, Huang SC, Chen ST, Yi-Chung Lin J, Chang YW, Chiang CY, Wen LL, Chan DC, Liu YC, Chen YJ (2004) Identification of tumor-associated plasma biomarkers using proteomic techniques: from mouse to human. Proteomics 4(9):2766–2775. doi: 10.1002/pmic.200400785 PubMedGoogle Scholar
  68. 68.
    Thompson LJ, Wang F, Proia AD, Peters KG, Jarrold B, Greis KD (2003) Proteome analysis of the rat cornea during angiogenesis. Proteomics 3(11):2258–2266. doi: 10.1002/pmic.200300498 PubMedGoogle Scholar
  69. 69.
    Fujii K, Nakano T, Kanazawa M, Akimoto S, Hirano T, Kato H, Nishimura T (2005) Clinical-scale high-throughput human plasma proteome analysis: lung adenocarcinoma. Proteomics 5(4):1150–1159. doi: 10.1002/pmic.200401145 PubMedGoogle Scholar
  70. 70.
    Soltys SG, Le QT, Shi G, Tibshirani R, Giaccia AJ, Koong AC (2004) The use of plasma surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic patterns for detection of head and neck squamous cell cancers. Clin Cancer Res 10(14):4806–4812. doi: 10.1158/1078-0432.CCR-03-0469 PubMedGoogle Scholar
  71. 71.
    Pang S, Smith J, Onley D, Reeve J, Walker M, Foy C (2005) A comparability study of the emerging protein array platforms with established ELISA procedures. J Immunol Methods 302(1–2):1–12. doi: 10.1016/j.jim.2005.04.007 PubMedGoogle Scholar
  72. 72.
    Liu MY, Xydakis AM, Hoogeveen RC, Jones PH, Smith EO, Nelson KW, Ballantyne CM (2005) Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome in human plasma, using the Luminex-100 system. Clin Chem 51(7):1102–1109. doi: 10.1373/clinchem.2004.047084 PubMedGoogle Scholar
  73. 73.
    Dupont NC, Wang K, Wadhwa PD, Culhane JF, Nelson EL (2005) Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol 66(2):175–191PubMedGoogle Scholar
  74. 74.
    Gerritsen ME, Soriano R, Yang S, Ingle G, Zlot C, Toy K, Winer J, Draksharapu A, Peale F, Wu TD, Williams PM (2002) In silico data filtering to identify new angiogenesis targets from a large in vitro gene profiling data set. Physiol Genomics 10(1):13–20PubMedGoogle Scholar
  75. 75.
    Peale FV Jr, Gerritsen ME (2001) Gene profiling techniques and their application in angiogenesis and vascular development. J Pathol 195(1):7–19. doi: 10.1002/path.888 PubMedGoogle Scholar
  76. 76.
    Ogawa S (1990) MRI of blood vessels at high fields: in vivo and in vitro measurements and image simulation. Magn Reson Med 16:9–18. doi: 10.1002/mrm.1910160103 PubMedGoogle Scholar
  77. 77.
    Abramovitch R, Frenkiel D, Neeman M (1998) Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging. Magn Reson Med 39(5):813–824. doi: 10.1002/mrm.1910390519 PubMedGoogle Scholar
  78. 78.
    Carmeliet P, Dor Y, Herbert J-M, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshet E (1998) Role of HIF-1 in hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. Nature 394:485–490. doi: 10.1038/28867 PubMedGoogle Scholar
  79. 79.
    Weisskoff RM (1999) Basic theoretical models of bold signal change. In: Moonen CTW, Bandettini PA (eds) Functional MRI. Springer, Heidelberg, pp 115–125Google Scholar
  80. 80.
    Pathak AP, Rand SD, Schmainda KM (2003) The effect of brain tumor angiogenesis on the in vivo relationship between the gradient-echo relaxation rate change (DeltaR2*) and contrast agent (MION) dose. J Magn Reson Imaging 18(4):397–403. doi: 10.1002/jmri.10371 PubMedGoogle Scholar
  81. 81.
    Silva AC, Kim S-G, Garwood M (2000) Imaging blood flow in brain tumors using arterial spin labeling. Magn Reson Med 44:169–173. doi:10.1002/1522-2594(200008)44:2<169::AID-MRM1>3.0.CO;2-UPubMedGoogle Scholar
  82. 82.
    Weber MA, Thilmann C, Lichy MP, Gunther M, Delorme S, Zuna I, Bongers A, Schad LR, Debus J, Kauczor HU, Essig M, Schlemmer HP (2004) Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: initial results. Invest Radiol 39(5):277–287. doi: 10.1097/01.rli.0000119195.50515.04 PubMedGoogle Scholar
  83. 83.
    Lauffer RB (1987) Paramagnetic metal complexes as water proton relaxation agents for nmr imaging: theory and design. Chem Rev 87:901–927. doi: 10.1021/cr00081a003 Google Scholar
  84. 84.
    Tofts PS (1997) Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 7:91–101. doi: 10.1002/jmri.1880070113 PubMedGoogle Scholar
  85. 85.
    Hacklander T, Reichenbach JR, Hofer M, Modder U (1996) Measurement of cerebral blood volume via the relaxing effect low-dose gadopentetate dimeglumine during bolus transit. AJNR Am J Neuroradiol 17:821–830PubMedGoogle Scholar
  86. 86.
    Donahue KM, Krouwer HG, Rand SD, Pathak AP, Marszalkowski CS, Censky SC, Prost RW (2000) Utility of simultaneously acquired gradient-echo and spin-echo cerebral blood volume and morphology maps in brain tumor patients. Magn Reson Med 43(6):845–853. doi:10.1002/1522-2594(200006)43:6<845::AID-MRM10>3.0.CO;2-JPubMedGoogle Scholar
  87. 87.
    Dennie J, Mandeville JB, Boxerman JL, Packard SD, Rosen BR, Weisskoff RM (1998) NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med 40:793–799. doi: 10.1002/mrm.1910400602 PubMedGoogle Scholar
  88. 88.
    Tropres I, Grimault S, Vaeth A, Grillon E, Julien C, Payen JF, Lamalle L, Decorps M (2001) Vessel size imaging. Magn Reson Med 45(3):397–408. doi:10.1002/1522-2594(200103)45:3<397::AID-MRM1052>3.0.CO;2-3PubMedGoogle Scholar
  89. 89.
    Maeda M, Itoh S, Kimura H, Iwasaki T, Hayashi N, Yamamoto K, Ishii Y, Kubota T (1993) Tumor vascularity in the brain: evaluation with dynamic susceptibility-contrast MR imaging. Radiology 189:233–238PubMedGoogle Scholar
  90. 90.
    Schmainda KM, Rand SD, Joseph AM, Lund R, Ward BD, Pathak AP, Ulmer JL, Badruddoja MA, Krouwer HG (2004) Characterization of a first-pass gradient-echo spin-echo method to predict brain tumor grade and angiogenesis. AJNR Am J Neuroradiol 25(9):1524–1532PubMedGoogle Scholar
  91. 91.
    Artemov D, Solaiyappan M, Bhujwalla ZM (2001) Magnetic resonance pharmacoangiography to detect and predict chemotherapy delivery to solid tumors. Cancer Res 61:3039–3044PubMedGoogle Scholar
  92. 92.
    Badruddoja MA, Krouwer HG, Rand SD, Rebro KJ, Pathak AP, Schmainda KM (2003) Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps. Neuro-oncol 5(4):235–243. doi: 10.1215/S1152851703000073 PubMedGoogle Scholar
  93. 93.
    Pathak A, Schmainda K, Ward B, Linderman J, Rebro KJ, Greene AS (2001) MR-derived cerebral blood volume maps: issues regarding histological validation and assessment of tumor angiogenesis. Magn Reson Med 46(4):735–747. doi: 10.1002/mrm.1252 PubMedGoogle Scholar
  94. 94.
    Schwarzbauer C, Syha J, Haase A (1993) Quantification of regional cerebral blood volumes by rapid T1 mapping. Magn Reson Med 29:709–712. doi: 10.1002/mrm.1910290521 PubMedGoogle Scholar
  95. 95.
    Brasch R, Pham C, Shames D et al (1997) Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging 7:68–74. doi: 10.1002/jmri.1880070110 PubMedGoogle Scholar
  96. 96.
    Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7PubMedGoogle Scholar
  97. 97.
    Donahue KM, Weisskoff RM, Burstein D (1997) Water diffusion and exchange as they influence contrast enhancement. J Magn Reson Imaging 7(1):102–110. doi: 10.1002/jmri.1880070114 PubMedGoogle Scholar
  98. 98.
    Kim YR, Rebro KJ, Schmainda KM (2002) Water exchange and inflow affect the accuracy of T1-GRE blood volume measurements: implications for the evaluation of tumor angiogenesis. Magn Reson Med 47(6):1110–1120. doi: 10.1002/mrm.10175 PubMedGoogle Scholar
  99. 99.
    Gossmann A, Helbich TH, Kuriyama N, Ostrowitzki S, Roberts TP, Shames DM, van Bruggen N, Wendland MF, Israel MA, Brasch RC (2002) Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiforme. J Magn Reson Imaging 15(3):233–240. doi: 10.1002/jmri.10072 PubMedGoogle Scholar
  100. 100.
    Bhujwalla ZM, Artemov D, Natarajan K, Kristjansen (2001) PEG Anti-angiogenic agent TNP-470 significantly decreases permeable regions. in 9th annual meeting, International society of magnetic resonance in medicine, Glasgow, ScotlandGoogle Scholar
  101. 101.
    Bhujwalla ZM, Artemov D, Natarajan K, Ackerstaff E, Solaiyappan M (2001) Vascular differences detected by mri for metastatic versus nonmetastatic breast and prostate cancer xenografts. Neoplasia 3(2):143–153. doi: 10.1038/sj.neo.7900129 PubMedGoogle Scholar
  102. 102.
    Artemov D (2003) Molecular magnetic resonance imaging with targeted contrast agents. J Cell Biochem 90(3):518–524. doi: 10.1002/jcb.10660 PubMedGoogle Scholar
  103. 103.
    Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, Lacy EK, Zhang H, Robertson JD, Wickline SA, Lanza GM (2003) 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 63(18):5838–5843PubMedGoogle Scholar
  104. 104.
    Morawski AM, Lanza GA, Wickline SA (2005) Targeted contrast agents for magnetic resonance imaging and ultrasound. Curr Opin Biotechnol 16(1):89–92. doi: 10.1016/j.copbio.2004.11.001 PubMedGoogle Scholar
  105. 105.
    Kang HW, Josephson L, Petrovsky A, Weissleder R, Bogdanov A Jr (2002) Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem 13(1):122–127. doi: 10.1021/bc0155521 PubMedGoogle Scholar
  106. 106.
    Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KCP (1998) Detection of tumor angiogenesis in vivo by AB-targeted magnetic resonance imaging. Nat Med 4(5):623–626. doi: 10.1038/nm0598-623 PubMedGoogle Scholar
  107. 107.
    Sipkins DA, Gijbels K, Tropper FD, Bednarski M, Li KC, Steinman L (2000) ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging. J Neuroimmunol 104(1):1–9. doi: 10.1016/S0165-5728(99)00248-9 PubMedGoogle Scholar
  108. 108.
    Yu X, Song SK, Chen J, Scott MJ, Fuhrhop RJ, Hall CS, Gaffney PJ, Wickline SA, Lanza GM (2000) High-resolution MRI characterization of human thrombus using a novel fibrin-targeted paramagnetic nanoparticle contrast agent. Magn Reson Med 44(6):867–872. doi:10.1002/1522-2594(200012)44:6<867::AID-MRM7>3.0.CO;2-PPubMedGoogle Scholar
  109. 109.
    Schirner M, Menrad A, Stephens A, Frenzel T, Hauff P, Licha K (2004) Molecular imaging of tumor angiogenesis. Ann N Y Acad Sci 1014:67–75. doi: 10.1196/annals.1294.007 PubMedGoogle Scholar
  110. 110.
    Santimaria M, Moscatelli G, Viale GL, Giovannoni L, Neri G, Viti F, Leprini A, Borsi L, Castellani P, Zardi L, Neri D, Riva P (2003) Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. Clin Cancer Res 9(2):571–579PubMedGoogle Scholar
  111. 111.
    Leong-Poi H, Christiansen J, Klibanov AL, Kaul S, Lindner JR (2003) Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 107(3):455–460. doi: 10.1161/01.CIR.0000044916.05919.8B PubMedGoogle Scholar
  112. 112.
    Fleischer AC, Donnelly EF, Grippo RJ, Black AS, Hallahan DE (2004) Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor. J Ultrasound Med 23(1):37–41PubMedGoogle Scholar
  113. 113.
    Cuccia DJ, Bevilacqua F, Durkin AJ, Merritt S, Tromberg BJ, Gulsen G, Yu H, Wang J, Nalcioglu O (2003) In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration. Appl Opt 42(16):2940–2950. doi: 10.1364/AO.42.002940 PubMedGoogle Scholar
  114. 114.
    Padera TP, Stoll BR, So PT, Jain RK (2002) Conventional and high-speed intravital multiphoton laser scanning microscopy of microvasculature, lymphatics, and leukocyte-endothelial interactions. Mol Imaging 1(1):9–15. doi: 10.1162/153535002753395662 PubMedGoogle Scholar
  115. 115.
    Brown E, McKee T, diTomaso E, Pluen A, Seed B, Boucher Y, Jain RK (2003) Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation. Nat Med 9(6):796–800. doi: 10.1038/nm879 PubMedGoogle Scholar
  116. 116.
    Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, Mohler WA (2002) Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys J 82(1 Pt 1):493–508PubMedCrossRefGoogle Scholar
  117. 117.
    Dafni H, Gilead A, Nevo N, Eilam R, Harmelin A, Neeman M (2003) Modulation of the pharmacokinetics of macromolecular contrast material by avidin chase: MRI, optical, and inductively coupled plasma mass spectrometry tracking of triply labeled albumin. Magn Reson Med 50(5):904–914. doi: 10.1002/mrm.10638 PubMedGoogle Scholar
  118. 118.
    Jain RK, Munn LL, Fukumura D (2002) Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2(4):266–276. doi: 10.1038/nrc778 PubMedGoogle Scholar
  119. 119.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5(3):161–171. doi: 10.1038/nrc1566 PubMedGoogle Scholar
  120. 120.
    Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2(1):11–18. doi: 10.1038/nrc701 PubMedGoogle Scholar
  121. 121.
    Smith JD, Fisher GW, Waggoner AS, Campbell PG (2007) The use of quantum dots for analysis of chick CAM vasculature. Microvasc Res 73(2):75–83. doi: 10.1016/j.mvr.2006.09.003 PubMedGoogle Scholar
  122. 122.
    Stroh M, Zimmer JP, Duda DG, Levchenko TS, Cohen KS, Brown EB, Scadden DT, Torchilin VP, Bawendi MG, Fukumura D, Jain RK (2005) Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11(6):678–682. doi: 10.1038/nm1247 PubMedGoogle Scholar
  123. 123.
    Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11(1):83–95. doi: 10.1016/j.ccr.2006.11.021 PubMedGoogle Scholar
  124. 124.
    Pasqualini R, Arap W, McDonald DM (2002) Probing the structural and molecular diversity of tumor vasculature. Trends Mol Med 8(12):563–571. doi: 10.1016/S1471-4914(02)02429-2 PubMedGoogle Scholar
  125. 125.
    Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do KA, Logothetis CJ, Pasqualini R (2002) Steps toward mapping the human vasculature by phage display. Nat Med 8(2):121–127. doi: 10.1038/nm0202-121 PubMedGoogle Scholar
  126. 126.
    Pasqualini R, Ruoslahti E (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380(6572):364–366. doi: 10.1038/380364a0 PubMedGoogle Scholar
  127. 127.
    Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279(5349):377–380. doi: 10.1126/science.279.5349.377 PubMedGoogle Scholar
  128. 128.
    Joyce JA, Laakkonen P, Bernasconi M, Bergers G, Ruoslahti E, Hanahan D (2003) Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis. Cancer Cell 4(5):393–403. doi: 10.1016/S1535-6108(03)00271-X PubMedGoogle Scholar
  129. 129.
    Segal E, Friedman N, Kaminski N, Regev A, Koller D (2005) From signatures to models: understanding cancer using microarrays. Nat Genet 37(Suppl):S38–S45. doi: 10.1038/ng1561 PubMedGoogle Scholar
  130. 130.
    West M, Ginsburg GS, Huang AT, Nevins JR (2006) Embracing the complexity of genomic data for personalized medicine. Genome Res 16(5):559–566. doi: 10.1101/gr.3851306 PubMedGoogle Scholar
  131. 131.
    Lamb J (2007) The connectivity map: a new tool for biomedical research. Nat Rev Cancer 7(1):54–60. doi: 10.1038/nrc2044 PubMedGoogle Scholar
  132. 132.
    Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5):427–434. doi: 10.1056/NEJMoa021491 PubMedGoogle Scholar
  133. 133.
    Rugo HS (2004) Bevacizumab in the treatment of breast cancer: rationale and current data. Oncologist 9(Suppl 1):43–49. doi: 10.1634/theoncologist.9-suppl_1-43 PubMedGoogle Scholar
  134. 134.
    Khurana R, Simons M (2003) Endothelial progenitor cells: precursors for angiogenesis. Semin Thorac Cardiovasc Surg 15(3):250–258. doi: 10.1016/S1043-0679(03)70004-5 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Arvind P. Pathak
    • 1
  • Warren E. Hochfeld
    • 2
  • Simon L. Goodman
    • 3
  • Michael S. Pepper
    • 2
    • 4
  1. 1.JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science and Department of OncologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Immunology, Faculty of Health SciencesUniversity of PretoriaPretoriaSouth Africa
  3. 3.Therapeutic Area Oncology - Preclinical ResearchMerck KGaADarmstadtGermany
  4. 4.Département de Médecine Génétique et DéveloppementUniversity Medical CenterGenevaSwitzerland

Personalised recommendations