Abstract
Antiangiogenic and antivascular agents provide new approaches to treating tumours. These may avoid many of the problems experienced with current approaches such as inherent and acquired resistance to treatment. Tumours do not grow beyond 1–2 mm3 in size without the development of new vessels (Folkman, 1971). Such neo-vascularization (angiogenesis) allows tumour cells to increase their nutrient supply, survive and proliferate despite the new vessels often having structural and functional differences compared to normal tissue vasculature. Treatments targeted at tumour vasculature have produced impressive results in animal models (Lindsay et al, 1996; Watson et al, 1996; O’Reilly, 1997; Horsman et al, 1998). These therapies are now entering clinical trials. However, the successful introduction of these therapies into clinical practice will require the development of reliable ways to assess angiogenesis and its modification or inhibition in vivo. Here we discuss some of the emerging imaging techniques that may be useful. © 2001 Cancer Research Campaign http://www.bjcancer.com
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16 November 2011
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References
Anderson H, Yap J and Price P (2000) Measurement of tumour and normal tissue (NT) perfusion by positron emission tomography (PET) in the evaluation of antivascular therapy: Results in the Phase I study of Combretastatin A4 Phosphate (CA4P). Proceedings of ASCO 19: 695
Araujo LI, Lammertsma AA, Rhodes CG, McFalls EO, Iida H, Rechavia E, Galassi A, de Silva R, Jones T and Maseri A (1991) Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation 83: 875–885
Aronen HJ, Gazit IE, Louis DN, Buchbinder BR, Pardo FS, Weisskoff RM, Harsh GR, Cosgrove GR, Halpern EF and Hochberg FH (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191: 41–51
Atkinson D, Brant-Zawadzki M, Gillan G, Purdy D and Laub G (1994) Improved MR angiography: magnetization transfer suppression with variable flip angle excitation and increased resolution. Radiology 190: 890–894
Axel L (1986) Blood flow effects in magnetic resonance imaging. Magn Reson Annu, 237–244
Blomley MJ, Coulden R, Bufkin C, Lipton MJ and Dawson P (1993) Contrast bolus dynamic computed tomography for the measurement of solid organ perfusion. Invest Radiol 8 (Suppl 5): S72–S77
Boetes C, Barentsz JO, Mus RD, van der Sluis RF, van Erning LJ, Hendriks JH, Holland R and Ruys SH (1994) MR characterization of suspicious breast lesions with a gadolinium-enhanced TurboFLASH subtraction technique. Radiology 193: 777–781
Boxerman JL, Hamberg LM, Rosen BR and Weisskoff RM (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34: 555–566
Brasch R, Pham C, Shames D, Roberts T, van Dijke K, van Bruggen N, Mann J, Ostrowitzki S and Melnyk O (1997) Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging 7: 68–74
Brix G, Semmler W, Port R, Schad LR, Layer G and Lorenz WJ (1991) Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr 15: 621–628
Burns PN, Halliwell M, Wells PN and Webb AJ (1982) Ultrasonic Doppler studies of the breast. Ultrasound Med Biol 8: 127–143
Crew JP, O’Brien T, Bicknell R, Fuggle S, Cranston D and Harris AL (1999) Urinary vascular endothelial growth factor and its correlation with bladder cancer recurrence rates [see comments]. J Urol 161: 799–804
Davies MM, Jonas SK, Kaur S and Allen-Mersh TG (2000) Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver mestastasis vascularity and volume. British Journal of Cancer 82: 1004–1008
Delorme S and Knopp MV (1998) Non-invasive vascular imaging: assessing tumour vascularity. Eur Radiol 8: 517–527
Dumoulin CL and Hart HRJ (1986) Magnetic resonance angiography. Radiology 161: 717–720
Emoto M, Iwasaki H, Mimura K, Kawarabayashi T and Kikuchi M (1997) Differences in the angiogenesis of benign and malignant ovarian tumors, demonstrated by analyses of color Doppler ultrasound, immunohistochemistry, and microvessel density. Cancer 80: 899–907
Ferrara N (1996) Vascular endothelial growth factor. European Journal of Cancer 32A: 2413–2422
Fisel CR, Ackerman JL, Buxton RB, Garrido L, Belliveau JW, Rosen BR and Brady TJ (1991) MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology. Magn Reson Med 17: 336–347
Fobben ES, Rubin CZ, Kalisher L, Dembner AG, Seltzer MH and Santoro EJ (1995) Breast MR imaging with commercially available techniques: radiologic-pathologic correlation. Radiology 196: 143–152
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186
Gasparini G (1996) Clinical significance of the determination of angiogenesis in human breast cancer: update of the biological background and overview of the Vicenza studies. Eur J Cancer 32A: 2485–2493
Harvey CJ, Blomley MJ, Eckersley RJ, Heckemann RA, Butler-Barnes J and Cosgrove DO (2000) Pulse-inversion mode imaging of liver specific microbubbles: improved detection of subcentimetre metastases [letter]. Lancet 355: 807–808
Harvey CJ, Blomley MJ and Dawson P Functional CT images of the acute hyperemic response to radiation of the prostate gland: early experience. J Comput Assist Tomogr 25: 43–49
Hawighorst H, Knapstein PG, Knopp MV, Weikel W, Brix G, Zuna I, Schonberg SO, Essig M, Vaupel P and van Kaick G (1998) Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival. Cancer Res 58: 3598–3602
Hermans R, Lambin P, Van den Bogaert W, Haustermans K, Van der Goten A and Baert AL (1997) Non-invasive tumour perfusion measurement by dynamic CT: preliminary results. Radiother Oncol 44: 159–162
Heywang SH, Wolf A, Pruss E, Hilbertz T, Eiermann W and Permanetter W (1989) MR imaging of the breast with Gd-DTPA: use and limitations. Radiology 171: 95–103
Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995) Pharmacokinetic mapping of the breast: a new method for dynamic MR mammography. Magn Reson Med 33: 506–514
Horsman MR, Ehrnrooth E, Ladekarl M and Overgaard J (1998) The effect of combretastatin A-4 disodium phosphate in a C3H mouse mammary carcinoma and a variety of murine spontaneous tumors. Int J Radiat Oncol Biol Phys 42: 895–898
Haubner R (2001) Non invasive imaging of αvβ3integrin expression using118F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 61: 1781–1785
Hulka CA, Edmister WB, Smith BL, Tan L, Sgroi DC, Campbell T, Kopans DB and Weisskoff RM (1997) Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis. Radiology 205: 837–842
Jain RK (1988) Determinants of tumor blood flow: a review. Cancer Res 48: 2641–2658
Kaiser WA (1993) [MR mammography] MR-Mammographie. Radiologe 33: 292–299
Kaiser WA (1994) False-positive results in dynamic MR mammography. Causes, frequency, and methods to avoid. Magn Reson Imaging Clin N Am 2: 539–555
Karczmar GS, River JN, Li J, Vijayakumar S, Goldman Z and Lewis MZ (1994) Effects of hyperoxia on T2* and resonance frequency weighted magnetic resonance images of rodent tumours. NMR Biomed 7: 3–11
Kerslake RW, Carleton PJ, Fox JN, Imrie MJ, Cook AM, Read JR, Bowsley SJ, Buckley DL and Horsman A (1995) Dynamic gradient-echo and fat-suppressed spin-echo contrast-enhanced MRI of the breast [see comments]. Clin Radiol 50: 440–454
Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, Krohn KA and Griffin TW (1992) Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys 22: 199–212
Koh WJ, Bergman KS, Rasey JS, Peterson LM, Evans ML, Graham MM, Grierson JR, Lindsley KL, Lewellen TK and Krohn KA (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: 391–398
Konig H, Sieper J and Wolf KJ (1990) Rheumatoid arthritis: evaluation of hypervascular and fibrous pannus with dynamic MR imaging enhanced with Gd-DTPA. Radiology 176: 473–477
Kouwenhoven M (1997) Contrast-enhanced MR angiography. Methods, limitations and possibilities. Acta Radiol Suppl 412: 57–67
Kuwatsuru R, Shames DM, Muhler A, Mintorovitch J, Vexler V, Mann JS, Cohn F, Price D, Huberty J and Brasch RC (1993) Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging. Magn Reson Med 30: 76–81
Lammertsma AA, Wise RJ and Jones T (1983) In vivo measurements of regional cerebral blood flow and blood volume in patients with brain tumours using positron emission tomography. Acta Neurochir (Wien) 69: 5–13
Lammertsma AA, Cunningham VJ, Deiber MP, Heather JD, Bloomfield PM, Nutt J, Frackowiak RS and Jones T (1990) Combination of dynamic and integral methods for generating reproducible functional CBF images. J Cereb Blood Flow Metab 10: 675–686
Leenders KL (1994) PET: blood flow and oxygen consumption in brain tumors. J Neurooncol 22: 269–273
Lindsay CK, Gomez DE and Thorgeirsson UP (1996) Effect of flavone acetic acid on endothelial cell proliferation: evidence for antiangiogenic properties. Anticancer Res 16: 425–431
Martinoli C, Derchi LE, Rizzatto G and Solbiati L (1998) Power Doppler sonography: general principles, clinical applications, and future prospects. Eur Radiol 8: 1224–1235
Mayr NA, Yuh WT, Magnotta VA, Ehrhardt JC, Wheeler JA, Sorosky JI, Davis CS, Wen BC, Martin DD, Pelsang RE, Buller RE, Oberley LW, Mellenberg DE and Hussey DH (1996) Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay. Int J Radiat Oncol Biol Phys 36: 623–633
McCoy CL, Parkins CS, Chaplin DJ, Griffiths JR, Rodrigues LM and Stubbs M (1995) The effect of blood flow modification on intra-and extracellular pH measured by 31P magnetic resonance spectroscopy in murine tumours. Br J Cancer 72: 905–911
Miles KA, Leggett DA, Kelley BB, Hayball MP, Sinnatamby R and Bunce I (1998) In vivo assessment of neovascularization of liver metastases using perfusion CT [see comments]. Br J Radiol 71: 276–281
Mountford RA and Atkinson P (1979) Doppler ultrasound examination of pathologically enlarged lymph nodes. Br J Radiol 52: 464–467
Nielsen FU, Topp S, Horsman MR, Overgaard J, Stodkilde-Jorgensen H and Maxwell RJ (1999) Localized in vivo 1H NMR spectroscopy of murine tumours: effect of blood flow reduction. NMR Biomed 12: 175–183
O’Reilly MS (1997) Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth. EXS 79: 273–294
Ogawa S, Lee TM, Kay AR and Tank DW (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci USA 87: 9868–9872
Orel SG, Schnall MD, LiVolsi VA and Troupin RH (1994) Suspicious breast lesions: MR imaging with radiologic-pathologic correlation. Radiology 190: 485–493
Parker GJ, Suckling J, Tanner SF, Padhani AR, Revell PB, Husband JE and Leach MO (1997) Probing tumor microvascularity by measurement, analysis and display of contrast agent uptake kinetics. J Magn Reson Imaging 7: 564–574
Perman WH, Heiberg EV and Herrmann VM (1996) Half-Fourier, three- dimensional technique for dynamic contrast-enhanced MR imaging of both breasts and axillae: initial characterization of breast lesions. Radiology 200: 263–269
Peters-Engl C, Medl M, Mirau M, Wanner C, Bilgi S, Sevelda P and Obermair A (1998) Color-coded and spectral Doppler flow in breast carcinomas – relationship with the tumor microvasculature. Breast Cancer Res Treat 47: 83–89
Postema S, Pattynama PM, Broker S, van der Geest RJ, van Rijswijk CS and Baptist TJ (1998) Fast dynamic contrast-enhanced colour-coded MRI in uterine cervix carcinoma: useful for tumour staging?. Clin Radiol 53: 729–734
Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM and Krohn KA (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18F] fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36: 417–428
Reeder SB, Atalay MK, McVeigh ER, Zerhouni EA and Forder JR (1996) Quantitative cardiac perfusion: a noninvasive spin-labeling method that exploits coronary vessel geometry. Radiology 200: 177–184
Roberts TP (1997) Physiologic measurements by contrast-enhanced MR imaging: expectations and limitations. J Magn Reson Imaging 7: 82–90
Robinson SP, Howe FA and Griffiths JR (1995) Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging [see comments]. Int J Radiat Oncol Biol Phys 33: 855–859
Robinson SP, Howe FA, Stubbs M and Griffiths JR (2000) Effects of nicotinamide and carbogen on tumour oxygenation, blood flow, energetics and blood glucose levels. Br J Cancer 82: 2007–2014
Rosen BR, Belliveau JW, Vevea JM and Brady TJ (1990) Perfusion imaging with NMR contrast agents. Magn Reson Med 14: 249–265
Shames DM, Kuwatsuru R, Vexler V, Muhler A and Brasch RC (1993) Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative noninvasive technique. Magn Reson Med 29: 616–622
Sterns EE, SenGupta S, Saunders F and Zee B (1996) Vascularity demonstrated by Doppler ultrasound and immunohistochemistry in invasive ductal carcinoma of the breast. Breast Cancer Res Treat 40: 197–203
Stubbs M (1999) Application of magnetic resonance techniques for imaging tumour physiology. Acta Oncol 38: 845–853
Su MY, Jao JC and Nalcioglu O (1994) Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI. Magn Reson Med 32: 714–724
Tofts PS and Kermode AG (1991) Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17: 357–367
Toi M, Hoshina S, Takayanagi T and Tominaga T (1994) Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Japanese Journal of Cancer Research 85: 1045–1049
van Zijl PC, Eleff SM, Ulatowski JA, Oja JM, Ulug AM, Traystman RJ and Kauppinen RA (1998) Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging [see comments]. Nat Med 4: 159–167
Verstraete KL, De Deene Y, Roels H, Dierick A, Uyttendaele D and Kunnen M (1994) Benign and malignant musculoskeletal lesions: dynamic contrast-enhanced MR imaging–parametric “first-pass” images depict tissue vascularization and perfusion. Radiology 192: 835–843
Villringer A, Rosen BR, Belliveau JW, Ackerman JL, Lauffer RB, Buxton RB, Chao YS, Wedeen VJ and Brady TJ (1988) Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects. Magn Reson Med 6: 164–174
Wamil BD, Thurman GB, Sundell HW, DeVore RF, Wakefield G, Johnson DH, Wang YF and Hellerqvist CG (1997) Soluble E-selectin in cancer patients as a marker of the therapeutic efficacy of CM101, a tumor-inhibiting anti-neovascularization agent, evaluated in phase I clinical trial. J Cancer Res Clin Oncol 123: 173–179
Watson SA, Morris TM, Parsons SL, Steele RJ and Brown PD (1996) Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model. Br J Cancer 74: 1354–1358
Wedeen VJ, Meuli RA, Edelman RR, Geller SC, Frank LR, Brady TJ and Rosen BR (1985) Projective imaging of pulsatile flow with magnetic resonance. Science 230: 946–948
Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM and Kaul S (1998) Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 97: 473–483
Weissleder R, Cheng HC, Marecos E, Kwong K and Bogdanov AJ (1998) Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions. Eur J Cancer 34: 1448–1454
Wells PT, Halliwell M, Skidmore R, Webb AJ and Woodcock JP (1977) Tumour detection by ultrasonic Doppler blood-flow signals. Ultrasonics 15: 231–232
White DN and Cledgett PR (1978) Breast carcinoma detection by ultrasonic Doppler signals. Ultrasound Med Biol 4: 329–335
Wilson CB, Lammertsma AA, McKenzie CG, Sikora K and Jones T (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: 1592–1597
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Anderson, H., Price, P., Blomley, M. et al. Measuring changes in human tumour vasculature in response to therapy using functional imaging techniques. Br J Cancer 85, 1085–1093 (2001). https://doi.org/10.1054/bjoc.2001.2077
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DOI: https://doi.org/10.1054/bjoc.2001.2077
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