Abstract
Monoclonal antibodies, F(ab’)2 fragments and peptidic vectors have been clinically tested for systemic and locoregional treatment of malignant gliomas. Since these brain-intrinsic neoplasms are characterized by relentless tumor cell infiltration of normal brain parenchyma, targeting agents require diffusive properties in order to reach invading tumor cell clusters that migrate along vascular clefts and axonal pathways. Tumor uptake was significantly improved by using small peptidic hormone receptors, e.g. modified octreotide, following systemic injections as compared to macromolecules which only led to limited stabilization of the disease. More importantly, biodistribution was found to be superior following direct intratumoral injection by using these small drug-like radioconjugates. Rapid and extensive distribution within 30 minutes was observed in large tumors, even crossing the corpus callosum in bihemispheric lesions following injection of 2-3 ml of the radiopharmakon injected into the center of non-resected tumors. Distribution was far more extensive after direct intratumoral injection as compared to intracavitary injection after surgical debulking. Increased interstitial pressure gradients and the much larger and chaotic structure of the interstitial space of a tumor compared to the extremely tight architecture of normal brain tissue might explain this unexpected biodistribution pattern. Peptidic hormone vectors might become useful agents to deliver radiopharmaceuticals into human invasive gliomas.
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Akabani G, Cokgor I, Coleman RE, Gonzalez Trotter D, Wong TZ, Friedman HS, Friedman AH, Garcia-Turner A, Herndon JE, DeLong D, McLendon RE, Zhao XG, Pegram CN, Provenzale JM, Bigner DD, Zalutsky MR (2000) Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 8106 therapy. Int J Radiat Oncol Biol Phys 46: 947–958
Bakay L (1970) The extracellular space in brain tumours. I. Morphological considerations. Brain 93: 693–698
Bender H, Takahashi H, Adachi K, Belser P, Liang SH, Pre-wett M, Schrappe M, Sutter A, Rodeck U, Herlyn D (1992) Immunotherapy of human glioma xenografts with unlabeled, 131I-, or 125¨ª-labeled monoclonal antibody 425 to epidermal growth factor receptor. Cancer Res 52: 121–126
Camby I, Salmon I, Oiry C, Galleyrand JC, Nagy N, Danguy A, Brotchi J, Pasteels JL, Martinez J, Kiss R (1996) The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines. Neuropeptides 30: 433–437
Colapinto EV, Zalutsky MR, Archer GE, Noska MA, Friedman HS, Carrel S, Bigner DD (1990) Radioimmunotherapy of intracerebral human glioma xenografts with 1311-labeled F(ab’)2 fragments of monoclonal antibody Mel-14. Cancer Res 50: 1822–1827
Haldemann AR, Rosler H, Barth A, Waser B, Geiger L, Godoy N, Markwalder RV, Seiler RW, Sulzer M, Reubi JC (1995) Somatostatin receptor scintigraphy in central nervous system tumors: role of blood-brain barrier permeability. J Nucl Med 36: 403–410
Hamilton JF, Morrison PF, Chen MY, Harvey-White J, Pernaute RS, Phillips H, Oldfield E, Bankiewicz KS (2001) Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp Neurol 168: 155–161
Hennig IM, Laissue JA, Horisberger U, Reubi JC (1995) Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer 61: 786–792
Hopkins K, Chandler C, Bullimore J, Sandeman D, Coakham H, Kemshead JT (1995) A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates. Radiother Oncol 34: 121–131
Hopkins K, Chandler C, Eatough J, Moss T, Kemshead JT (1998) Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose. Int J Radiat Oncol Biol Phys 40: 835–844
Krewson CE, Klarman ML, Saltzman WM (1995) Distribution of nerve growth factor following direct delivery to brain interstitium. Brain Res 680: 196–206
Lamberts SW, Reubi JC, Krenning EP (1994) Somatostatin and the concept of peptide receptor scintigraphy in oncology. Semin Oncol 21: 1–5
Merlo A, Hausmann O, Wasner M, Steiner P, Otte A, Jermann E, Freitag P, Reubi JC, Muller-Brand J, Gratzl O, Macke HR (1999) Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTAO-DPhe 1 -Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res 5: 1025–1033
Merlo A, Jermann E, Hausmann O, Chiquet-Ehrismann R, Probst A, Landolt H, Maecke HR, Mueller-Brand J, Gratzl O (1997) Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas. Int J Cancer 71: 810–816
Netti PA, Berk DA, Swartz MA, Grodzinsky AJ, Jain RK (2000) Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res 60: 2497–2503
Nguyen TT, Pannu YS, Sung C, Dedrick RL, Walbridge S, Brechbiel MW, Garmestani K, Beitzel M, Yordanov AT, Old-field EH (2003) Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging. J Neurosurg 98: 584–590
Occhiogrosso G, Edgar MA, Sandberg DI, Souweidane MM (2003) Prolonged convection-enhanced delivery into the rat brainstem. Neurosurgery 52: 388–393; discussion 393–394
Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, Heppeler A, Mueller-Brand J, Maecke HR (1997) DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 24: 792–795
Pardridge WM, Frank HJ, Cornford EM, Braun LD, Crane PD, Oldendorf WH (1981) Neuropeptides and the blood-brain barrier. Adv Biochem Psychopharmacol 28: 321–328
Petrovich Z, Apuzzo MLJ, Luxton G, Jepson H, Cohen D (1988) Interstitial radiobrachytherapy of malignant cerebral gliomas. In: Kornblith PL, Walker MD (eds) Advances in neuro-oncology. Futura Publishing Co, New York, pp 387–414
Reubi JC, Horisberger U, Lang W, Koper JW, Braakman R, Lamberts SW (1989) Coincidence of EGF receptors and somatostatin receptors in meningiomas but inverse, differentiation-dependent relationship in glial tumors. Am J Pathol 134: 337–344
Riva P, Franceschi G, Riva N, Casi M, Santimaria M, Adamo M (2000) Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach. Eur J Nucl Med 27: 601–609
Schumacher T, Hofer S, Eichhorn K, Wasner M, Zimmerer S, Freitag P, Probst A, Gratzl O, Reubi JC, Maecke R, Mueller-Brand J, Merlo A (2002) Local injection of the 90Y-labelled peptidic vector DOTATOC to control gliomas of WHO grades II and III: an extended pilot study. Eur J Nucl Med Mol Imaging 29: 486–493
Tilmann S, Waldherr C, Mueller-Brand J, Maecke H (2002) Kidney failure after treatment with 90Y-DOTATOC. Eur J Nucl Med Mol Imaging 29: 435
Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J (2001) The clinical value of [90Y-DOTA]-D-PhelTyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 12: 941–945
Walker WL, Cook J (1996) Drug delivery to brain tumors. Bull Math Biol 58: 1047–1074
Zalutsky MR, Moseley RP, Benjamin JC, Colapinto EV, Fuller GN, Coakham HP, Bigner DD (1990) Monoclonal antibody and F(ab’)2 fragment delivery to tumor in patients with glioma: comparison of intracarotid and intravenous administration. Cancer Res 50: 4105–4110
Zalutsky MR, Moseley RP, Coakham HB, Coleman RE, Bigner DD (1989) Pharmacokinetics and tumor localization of 1311-labeled anti-tenascin monoclonal antibody 8106 in patients with gliomas and other intracranial malignancies. Cancer Res 49: 2807–2813
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Merlo, A., Mueller-Brandand, J., Maecke, H.R. (2003). Comparing monoclonal antibodies and small peptidic hormones for local targeting of malignant gliomas. In: Westphal, M., Tonn, JC., Ram, Z. (eds) Local Therapies for Glioma Present Status and Future Developments. Acta Neurochirurgica Supplements, vol 88. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6090-9_14
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DOI: https://doi.org/10.1007/978-3-7091-6090-9_14
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