Abstract
Glioblastoma multiforme (GBM) is the most malignant type of brain neoplasm with an average patient survival of 15 months under the current treatment regime. The failure of therapeutic approaches including surgical resections is due to multiple factors, including molecular diversity of GBMs, invading micro-metastases, presence of tumor stem cells, molecular drug resistance, as well as difficulties of delivering therapeutics across the vascular brain-tumor barrier. Non-invasive imaging of molecular make-up of GBM could facilitate the identification of critical disease features and tailoring of treatments to individual disease variants, respectively. Development of such molecular imaging agents requires integration of tumor biomarker discovery with the development of biomarker-targeting molecular imaging agents, and their validation in pre-clinical disease models. This chapter will describe processes and techniques involved in the pre-clinical development of molecular imaging agents for brain tumors, with the particular emphasis on workflows leading from biomarker selection to developing single-domain antibody-targeted imaging probes to visualize and evaluate biomarker expression by in vivo imaging using various imaging modalities.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Akaogi K, Okabe Y, Sato J, Nagashima Y, Yasumitsu H, Sugahara K, Miyazaki K (1996) Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells. Proc Natl Acad Sci USA 93:8384–8389
Bell A, Wang ZJ, Arbabi-Ghahroudi M, Chang TA, Durocher Y, Trojahn U, Baardsnes J, Jaramillo ML, Li S, Baral TN, O’Connor-McCourt M, Mackenzie R, Zhang J (2010) Differential tumor-targeting abilities of three single-domain antibody formats. Cancer Lett 289:81–90
Cai W, Chen K, Mohamedali KA, Cao Q, Gambhir SS, Rosenblum MG, Chen X (2006) PET of vascular endothelial growth factor receptor expression. J Nucl Med 47:2048–2056
Cormode DP, Jarzyna PA, Mulder WJ, Fayad ZA (2010) Modified natural nanoparticles as contrast agents for medical imaging. Adv Drug Deliv Rev 62:329–338
Di Marco M, Sadun C, Port M, Guilbert I, Couvreur P, Dubernet C (2007) Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents. Int J Nanomed 2:609–622
Doyle PJ, Arbabi-Ghahroudi M, Gaudette N, Furzer G, Savard ME, Gleddie S, McLean MD, Mackenzie CR, Hall JC (2008) Cloning, expression, and characterization of a single-domain antibody fragment with affinity for 15-acetyl-deoxynivalenol. Mol Immunol 45:3703–3713
Dumoulin M, Conrath K, Van Meirhaeghe A, Meersman F, Heremans K, Frenken LG, Muyldermans S, Wyns L, Matagne A (2002) Single-domain antibody fragments with high conformational stability. Protein Sci 11:500–515
Glogard C, Stensrud G, Hovland R, Fossheim SL, Klaveness J (2002) Liposomes as carriers of amphiphilic gadolinium chelates: the effect of membrane composition on incorporation efficacy and in vitro relaxivity. Int J Pharm 233:131–140
Gupta H, Weissleder R (1996) Targeted contrast agents in MR imaging. Magn Reson Imaging Clin N Am 4:171–184
Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, Bendahman N, Hamers R (1993) Naturally occurring antibodies devoid of light chains. Nature 363:446–448
Hamzah J, Altin JG, Herringson T, Parish CR, Hammerling GJ, O’Donoghue H, Ganss R (2009) Targeted liposomal delivery of TLR9 ligands activates spontaneous antitumor immunity in an autochthonous cancer model. J Immunol 183:1091–1098
Iqbal U, Albaghdadi H, Luo Y, Arbabi M, Desvaux C, Veres T, Stanimirovic D, Abulrob A (2010a) Molecular imaging of glioblastoma multiforme using anti-insulin-like growth factor-binding protein-7 single domain antibodies. Br J Cancer 103:1606–1616
Iqbal U, Trojahn U, Albaghdadi H, Zhang J, O’Connor-McCourt M, Stanimirovic D, Tomanek B, Sutherland G, Abulrob A (2010b) Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumors. Br J Pharm 160:1016–1028
Isaka T, Yoshimine T, Maruno M, Kuroda R, Ishii H, Hayakawa T (1994) Altered expression of antithrombotic molecules in human glioma vessels. Acta Neuropathol 87:81–85
Jain RK (1994) Barriers to drug delivery in solid tumors. Sci Am 271:58–65
Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8:610–622
Lauwereys M, Arbabi Ghahroudi M, Desmyter A, Kinne J, Hölzer W, De Genst E, Wyns L, Muyldermans S (1998) Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J 17:3512–3520
Machein MR, Kullmer J, Fiebich BL, Plate KH, Warnke PC (1999) Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors. Neurosurgery 44:732–740
Nagane M, Lin H, Cavenee WK, Huang HJ (2001) Aberrant receptor signaling in human malignant gliomas: mechanisms and therapeutic implications. Cancer Lett 162 Suppl:S17–S21
Nieh MP, Harroun TA, Raghunathan VA, Glinka CJ, Katsaras J (2003) Concentration independent spontaneously forming biomimetic vesicles. Phys Rev Lett 91:158105
Nieh MP, Harroun TA, Raghunathan VA, Glinka CJ, Katsaras J (2004) Spontaneously formed monodisperse biomimetic unilamellar vesicles: effect of charge, dilution and time. Biophys J 86:2615–2629
Nieh MP, Raghunathan VA, Kline SR, Harroun TA, Huang CY, Pence J, Katsaras J (2005) Spontaneously formed unilamellar vesicles with path dependent size distribution. Langmuir 21:6656–6661
Nishikawa R, Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ (1994) A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91:7727–7731
Pen A, Moreno MJ, Durocher Y, Deb-Rinker P, Stanimirovic DB (2008) Glioblastoma-secreted factors induce IGFPB7 and angiogenesis by modulating Smad-2-dependent TGF-β signalling. Oncogene 27:6834–6844
Pen A, Moreno MJ, Martin J, Stanimirovic DB (2007) Molecular markers of extracellular matrix remodelling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels. Glia 15:559–572
Reimer P, Tombach B (1998) Hepatic MRI with SPIO: detection and characterization of focal liver lesions. Eur Radiol 8:1198–1204
Roovers RC, van Dongen GA, van Bergen en Henegouwen PM (2007) Nanobodies in therapeutic applications. Curr Opin Mol Ther 9:327–335
Schnell O, Krebs B, Carlsen J, Miederer I, Goetz C, Goldbrunner RH, Wester HJ, Haubner R, Popperl G, Holtmannspotter M, Kretzschmar HA, Kessler H, Tonn JC, Schwaigner M, Beer AJ (2009) Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by 18F Galacto-RGD positron emission tomography. Neuro-oncology 6:861–870
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 289:1197–1202
Strijkers GJ, Kluza E, Van Tilborg GA, van der Schaft DW, Griffioen AW, Mulder WJ, Nicolay K (2010) Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis. Angiogenesis 13:161–173
Suwa T, Ozawa S, Ueda M, Ando N, Kitajima M (1998) Magnetic resonance imaging of esophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody. Int J Cancer 75:626–634
Thakur M, Lentle BC (2006) Report of a summit on molecular imaging. Am J Roentgenol 186:297–299
Tromsdorf UI, Bruns OT, Salmen SC, Beisiege U, Weller H (2009) A highly effective, nontoxic T1 MR contrast agent based on ultrasmall PEGylated iron oxide nanoparticles. Nano Lett 9:4434–4440
Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B (1987) Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84:6899–6903
Yue B, Huang CY, Nieh MP, Glinka CJ, Katasaras J (2005) Highly stable phospholipid unilamellar vesicles from spontaneous vesiculation: a DLS and SANS study. J Phys Chem 109:609–616
Zhang D, Feng XY, Henning TD, Wen L, Lu WY, Pan H, Wu X, Zou LG (2009) MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes targeted to CD105. Eur J Radiol 70:180–189
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Abulrob, A., Iqbal, U., Tomanek, B., Stanimirovic, D. (2012). Molecular Imaging of Brain Tumours Using Single Domain Antibodies. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 4. Tumors of the Central Nervous System, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1706-0_14
Download citation
DOI: https://doi.org/10.1007/978-94-007-1706-0_14
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-1705-3
Online ISBN: 978-94-007-1706-0
eBook Packages: MedicineMedicine (R0)