Abstract
Studies of the metastatic process and potential cancer therapies have been advanced by the use of imaging technology that enables the noninvasive assessment of tumor development over time. Several imaging modalities have been used to examine brain metastases in preclinical cancer models. Magnetic resonance imaging (MRI) is the clinical gold standard for anatomical evaluation of brain metastases. New advances in MRI and MR spectroscopy (MRS) have now enabled physiological characteristics of tumors to be investigated including tumor permeability, vascularity, cellularity and metabolism as well as cerebral blood flow and blood volume. MRI can also be used to detect single iron-labeled cancer cells after their initial arrest in mouse brain and subsequent tumor development. Nuclear imaging techniques including positron emission tomography (PET) and single photon emission computed tomography (SPECT) are popular tools for classifying tumors and monitoring their treatment. Brain tumors can be assessed for biochemical alterations such as glucose use, DNA synthesis, amino acid transport and oxygenation state. Optical imaging techniques based on the use of fluorescent or bioluminescent reporters have been found advantageous for monitoring metastatic tumor burden in experimental animals. Fluorescent entities have further been used in intravital microscopy to track and monitor the relationship between tumor cells and brain vasculature, including cancer cell arrest, early extravasation, perpetuation of a perivascular position and either angiogenesis or vessel co-option. Finally, imaging studies of brain metastases are often improved by using multiple imaging techniques concurrently, thereby exploiting the best features of separate modalities to acquire multilayered information and provide further insights into the evolution of metastases.
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References
Fidler IJ, Yano S, Zhang RD, Fujimaki T, Bucana CD (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3:53–57
Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2:683–693
Hoffman RM (2005) In vivo cell biology of cancer cells visualized with fluorescent proteins. Curr Top Dev Biol 70:121–144
Heyn C, Ronald JA, Ramadan SS et al (2006) In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 56:1001–1010
Kienast Y, von Baumgarten L, Fuhrmann M et al (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16(1):116–122
Close DM, Hahn RE, Patterson SS, Baek SJ, Ripp SA, Sayler GS (2011) Comparison of human optimized bacterial luciferase, firefly luciferase, and green fluorescent protein for continuous imaging of cell culture and animal models. J Biomed Opt 16(4):047003-1-10
Axelsson R, Bach-Gansmo T, Castell-Conesa J, McParland BJ et al (2010) An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αvβ3-selective angiogenesis imaging agent 99mTc-NC100692. Acta Radiol 51(1):40–46
Dierckx RA, Martin JJ, Dobbeleir A, Crols R, Neetens I, De Deyn PP (1994) Sensitivity and specificity of thallium-201 single-photon emission tomography in the functional detection and differential diagnosis of brain tumours. Eur J Nucl Med 21(7):621–633
Gambarota G, Leenders W (2011) Characterization of tumor vasculature in mouse brain by USPIO contrast-enhanced MRI. Methods Mol Biol 771:447–487
Budde MD, Gold E, Jordan EK, Frank JA (2012) Differential microstructure and physiology of brain and bone metastases in a rat breast cancer model by diffusion and dynamic contrast enhanced MRI. Clin Exp Metastasis 29(1):51–62
Budde MD, Gold E, Jordan EK, Smith-Brown M, Frank JA (2011) Phase contrast MRI is an early marker of micrometastatic breast cancer development in the rat brain. NMR Biomed 25(5):726–736
Kluetz PG, Meltzer CC, Villemange VL et al (2000) Combined PET/CT imaging in oncology. Impact on patient management. Clin Positron Imaging 3(6):223–230
Chen W (2007) Clinical applications of PET in brain tumors. J Nucl Med 48:1468–1481
Kaal ECA, Taphoorn MJB, Vecht CJ (2005) Symptomatic management and imaging of brain metastases. J Neurooncol 75:15–20
Leenders W, Küsters B, Pikkemaat J et al (2003) Vascular endothelial growth factor-a determines detectability of experimental melanoma brain metastasis in Gd-DTPA-enhanced MRI. Int J Cancer 105:437–443
Kemper EM, Leenders W, Küsters B et al (2006) Development of luciferase tagged brain tumour models in mice for chemotherapy intervention studies. Eur J Cancer 42:3294–3303
Simões RV, Martinez-Aranda A, Martín B, Cerdán S, Sierra A, Arús C (2008) Preliminary characterization of an experimental breast cancer cells brain metastasis mouse model by MRI/MRS. Magn Reson Mater Phy 21:237–249
Percy DB, Ribot EJ, Chen Y et al (2011) In vivo characterization of changing blood-tumor barrier permeability in a mouse model of breast cancer metastasis. A complementary magnetic resonance imaging approach. Invest Radiol 46:718–725
Law M, Cha S, Knopp EA, Johnson G, Arnett J, Litt AW (2002) High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging. Radiology 222(3):715–721
Chiang EC, Kuo YT, Lu CY et al (2004) Distinction between high-grade gliomas and solitary metastases using peritumoral 3-T magnetic resonance spectroscopy, diffusion, and perfusion imagings. Neuroradiology 46(8):619–627
Lignelli A, Khadji AG (2011) Review of imaging techniques in the diagnosis and management of brain metastases. Neurosurg Clin N Am 22:15–25
Gambarota G, Leenders W, Maass C et al (2008) Characterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI. Br J Cancer 98:1784–1789
Bulte JW, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17(7):484–499
Frank JA, Anderson SA, Kalsih H et al (2004) Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging. Cytotherapy 6:621–625
Moffat BA, Chenevert TL, Meyer CR et al (2006) The functional diffusion Map: an imaging biomarker for the early prediction of cancer treatment outcome. Neoplasia 8:259–267
Ross BD, Chenevert TL, Kim B, Ben-Joseph O (1994) Magnetic resonance imaging and spectroscopy: application to experimental neurooncology. J Magn Res Biol Med 1:89–106
Pilatus U, Aboagye E, Artemov D, Mori N, Ackerstaff E, Bhujwalla ZM (2001) Real-time measurements of cellular oxygen consumption, pH, and energy metabolism using nuclear magnetic resonance spectroscopy. Magn Reson Med 45(5):749–755
Kugel H, Heindel W, Ernestus RI, Bunke J, du Mesnil R, Friedmann G (1992) Human brain tumors: spectral patterns detected with localized H-1 MR spectroscopy. Radiology 183(3):701–709
Gajewicz W, Papierz W, Szymczak W, Goraj B (2003) The use of proton MRS in the differential diagnosis of brain tumors and tumor-like processes. Med Sci Monit 9(9):MT97–MT105
Poptani H, Gupta RK, Roy R, Pandey R, Jain VK, Chhabra DK (1995) Characterization of intracranial mass lesions with in vivo proton MR spectroscopy. Am J Neuroradiol 16(8):1593–1603
Schmall B, Conti PS, Schaeffer DJ, Kleinert EL (1992) Tumor and organ biochemical profiles determined in vivo following uptake of a combination of radiolabeled substrates: potential applications for PET. Am J Physiol Imaging 7(1):2–11
Conti PS (1995) Introduction to imaging brain tumor metabolism with positron emission tomography (PET). Cancer Invest 13(2):244–259
Di Chiro G (1987) Postiron emission tomography using [18 F] fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool. Invest Radiol 22:360–371
Di Chiro G, Oldfield E, Wright DC et al (1988) Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies. Am J Roentgenol 250:189–197
Kato T, Shinoda J, Nakayama N et al (2008) Metabolic assessment of gliomas using 11C-methionine, {18 F] fluorodeoxyglucose, and 11C-choline positron-emission tomography. Am J Neuroradiol 29(6):1176–1182
Lee HY, Chung J-K, Jeong JM et al (2008) Comparison of FDG-PET findings of brain metastasis from non-small-cell lung cancer and small-cell lung cancer. Ann Nucl Med 22:281–286
Prieto E, Martí-Climent JM, Domínguez-Prado I et al (2011) Voxel-based analysis of dual-time-point 18 F-FDG PET images for brain tumor identification and delineation. J Nucl Med 52:865–872
Coleman RE (2001) PET in lung cancer staging. Q J Nucl Med 45:231–250
Kamel EM, Zwahlen D, Wyss MT, Stumpe K, Schulthess GK, Steinert HC (2003) Whole-body 18 F-FDG PET improved the management of patients with small cell lung cancer. J Nucl Med 44:1911–1917
Munch-Petersen B, Cloos L, Jensen HK, Tyrsted G (1995) Human thymidine kinase 1. Regulation in normal and malignant cells. Adv Enzyme Regul 35:69–89
Seitz U, Wagner M, Neumaier B et al (2002) Evaluation of pyrimidine metabolizing enzymes and in vitro uptake of 3′-[(18)F]fluoro-3′-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines. Eur J Nucl Med Mol Imaging 29:1174–1181
Barwick T, Bencherif B, Mountz JM, Avril N (2009) Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation. Nucl Med Commun 30:908–917
Chen W, Cloughesy T, Kamdar N et al (2005) Imaging proliferation in brain tumors with 18 F-FLT PET: comparison with 18 F-FDG. J Nucl Med 46:945–952
Hatakeyama T, Kawai N, Nishiyama Y et al (2008) 11C-Methionine (MET) and 18 F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma. Eur J Nucl Med Mol Imaging 35:2009–2017
Miyagawa T, Oku T, Uehara H et al (1998) “Facilitated” amino acid transport is upregulated in brain tumors. J Cereb Blood Flow Metab 18:500–509
Rasey JS, Koh WJ, Evans ML et al (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18 F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36(2):417–428
Brown JM (2001) Therapeutic targets in radiotherapy. Int J Radiat Oncol Biol Phys 49(2):319–326
Wu AM, Yazaki PJ (2000) Designer Genes: recombinant antibody fragments for biological imaging. Q J Nucl Med 44(3):268–283
Kortt AA, Dolezal O, Power BE, Hudson PJ (2001) Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting. Biomol Eng 18:95–108
Rosenthal MS, Cullom J, Hawkins W, Moore SC, Tsui BM, Yester M (1995) Quantitative SPECT imaging: a review and recommendations by the focus committee of the society of nuclear medicine computer and instrumentation council. J Nucl Med 36(8):1489–1513
Kojima Y, Nobumasa K, Noji M, Tosa J (1994) Differentiation of malignant glioma and metastatic brain tumor by thallium-201 single photon emission computed tomography. Neurol Med Chir (Tokyo) 34:588–592
Ancri D, Basset JY, Londchamp MF, Etavard C (1978) Diagnosis of cerebral metastasis by thallium 201. Radiology 128:417–427
Yang M, Baranov E, Wang J-W et al (2002) Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model. Proc Natl Acad Sci 99(6):3824–3829
Yang M, Baranov E, Jiang P et al (2000) Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci 97(3):1206–1211
Jenkins DE, Hornig YS, Oei Y, Dusich J, Purchio T (2005) Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice. Breast Cancer Res 7:R444–R454
Liu T, Ding Y, Xie W et al (2007) An imageable metastatic treatment model of nasopharyngeal carcinoma. Clin Cancer Res 13(13):3960–3967
Chung E, Yamashita H, Au P, Tannous BA, Fukumura D, Jain RK (2009) Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS One 4(12):e8316
Song H-T, Jordan EK, Lewis BK et al (2009) Rat model of metastatic breast cancer monitored by MRI at 3 Tesla and bioluminescence imaging with histological correlation. J Transl Res 7:88
Palmieri D, Bronder JL, Herring JM et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67(9):4190–4198
Rozniecki JJ, Sahagian GG, Kempuraj D et al (2010) Brain metastases of mouse mammary adenocarcinoma is increased by acute stress. Brain Res 1366:204–210
Skultétyová I, Tokarev D, Jezová D (1998) Stress-induced increase in blood–brain barrier permeability in control and monosodium glutamate-treated rats. Brain Res Bull 45(2):175–178
Weigert R, Sramkova M, Parente L, Masedunskas A (2010) Intravital microscopy: a novel tool to study cell biology in living animals. Histochem Cell Biol 133(5):481–491
Carbonell WS, Ansorge O, Sibson N, Muschel R (2009) The vascular basement membrane as “soil” in brain metastasis. PLoS One 4(6):e5857
Brix G, Nekolla EA, Nosske D, Griebel J (2009) Risks and safety aspects related to PET/MR examinations. Eur J Nucl Med Mol Imaging 36(Suppl 1):131–138
von Schulthess G, Schlemmer H-P (2009) A look ahead: PET/MR versus PET/CT. Eur J Nucl Med Mol Imaging 36:3–9
Wehrl HF, Jedenhofer MS, Wiehr S, Pichler BJ (2009) Pre-clinical PET/MR: technological advances and new perspectives in biomedical research. Eur J Nucl Med Mol Imaging 36(Suppl 1):56–68
Lim E, Modi K, Christensen A, Meganck J, Oldfield S, Zhang N (2011) Monitoring tumor metastases and osteolytic lesions with bioluminescence and micro CT imaging. J Vis Exp (50):e2775
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Hamilton, A.M., Foster, P.J. (2012). Imaging Experimental Brain Metastases. In: Palmieri, D. (eds) Central Nervous System Metastasis, the Biological Basis and Clinical Considerations. Cancer Metastasis - Biology and Treatment, vol 18. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5291-7_5
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