Radioimmuntherapie maligner Gliome

Zusammenfassung

Trotz aller technischer Fortschritte (intraoperative Resektionskontrolle, fluoreszenzgestützte Operation, fortschrittliche Bestrahlungstechniken) und neuer Erkenntnisse in der systemischen Chemotherapie ist die Behandlung maligner Gliome mittels konventioneller Therapie (Operation, perkutane Bestrahlung und Chemotherapie) nach wie vor unbefriedigend. Eine radikale Tumorentfernung ist unmöglich, da Tumorzellen diffus in das umgebende Hirngewebe infiltrieren und jegliche Therapie durch die eingeschränkte Toleranz des umgebenden gesunden Hirngewebes limitiert ist. Neue Therapieansätze zielen daher auf eine zunehmend selektive Zerstörung von Tumorzellen ab. So exprimieren maligne Gliomzellen verschiedene Antigene oder Rezeptoren, die in gesundem Gewebe nicht oder nur in deutlich geringerem Maße vorkommen. Die Applikation radioaktiv markierter Antikörper, besonders nach lokaler Gabe, die gegen diese Zielstrukturen gerichtet sind, bietet daher einen innovativen Therapieansatz, der in vielen klinischen Phase-I- und -II-Studien bereits viel versprechende Ergebnisse bei akzeptablem Nebenwirkungsprofil gezeigt hat. Diese Übersichtsarbeit fasst eigene Erfahrungen und in der Literatur publizierte Daten zur Radioimmuntherapie maligner Gliome zusammen und zeigt mögliche zukünftige Entwicklungen zur Verbesserung dieser Therapieform auf.

Abstract

Despite all technical advances (intraoperative resection control, fluorescence guided resection, advances in external beam radiation techniques) and new consolidated findings on systemic chemotherapy treatment of malignant gliomas with conventional therapeutic modalities (surgery, radiation therapy and chemotherapy) is still highly unfavourable. Total tumor erradication is impossible due to tumor infiltrations into the normal brain and the limitations given by the limited tolerance of surrounding brain tissue. New treatment strategies, therefore, aim for a more selective destruction of tumor cells. Malignant glioma cells selectively express several antigens or receptors which are not or only to a minor extent present in normal brain tissue. Administration of radiolabelled monoclonal antibodies, especially when given locoregionally, targeting these tumor-specific antigens offers an innovative therapeutic strategy that has recently demonstrated encouraging antitumor effects and acceptable toxicity in many phase I / II clinical trials. This review offers a comprehensive summary of own experiences and results of clinical trials reported in the literature dealing with radioimmunotherapy of malignant glioma and highlights future plans to further develop this therapeutic strategy.

maligne Gliome - Radioimmuntherapie - intrakavitär / intratumoral - Tenascin-C

malignant gliomas - radioimmunotherapy - intracavitary / intratumoral - Tenascin C

Literatur

• 1 Akabani G, Reardon D A, Coleman R E, Wong T Z, Metzler S D, Bowsher J E, Barboriak D P, Provenzale J M, Greer K L, DeLong D, Friedman H S, Friedman A H, Zhao X G, Pegram C N, McLendon R E, Bigner D D, Zalutsky M R. Dosimetry and radiographic analysis of ¹³¹I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.  J Nucl Med. 2005;  46 1042-1051
• 2 Bartolomei M, Mazzetta C, Handkiewicz-Junak D, Bodei L, Rocca P, Grana C, Maira G, Sturiale C, Villa G, Paganelli G. Combined treatment of glioblastoma patients with locoregional pre-targeted ⁹⁰Y-biotin radioimmunotherapy and temozolomide.  Q J Nucl Med Mol Imaging. 2004;  48 220-228
• 3 Bigner D D, Brown M T, Friedman A H, Coleman R E, Akabani G, Friedman H S, Thorstad W L, McLendon R E, Bigner S H, Zhao X G, Pegram C N, Wikstrand C J, Herndon 2nd  J E, Vick N A, Paleologos N, Cokgor I, Provenzale J M, Zalutsky M R. Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results.  J Clin Oncol. 1998;  16 2202-2212
• 4 Boiardi A, Bartolomei M, Silvani A, Eoli M, Salmaggi A, Lamperti E, Milanesi I, Botturi A, Rocca P, Bodei L, Broggi G, Paganelli G. Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma.  J Neurooncol. 2005;  72 125-131
• 5 Brack S S, Silacci M, Birchler M, Neri D. Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C.  Clin Cancer Res. 2006;  12 3200-3208
• 6 Brady L W, Markoe A M, Woo D V, Amendola B E, Karlsson U L, Rackover M A, Koprowski H, Steplewski Z, Peyster R G. Iodine-125-labeled anti-epidermal growth factor receptor-425 in the treatment of glioblastoma multiforme. A pilot study.  Front Radiat Ther Oncol. 1990;  24 151-160 , discussion 161-165
• 7 Brady L W, Markoe A M, Woo D V, Rackover M A, Koprowski H, Steplewski Z, Peyster R G. Iodine125 labeled anti-epidermal growth factor receptor-425 in the treatment of malignant astrocytomas. A pilot study.  J Neurosurg Sci. 1990;  34 243-249
• 8 Cokgor I, Akabani G, Kuan C T, Friedman H S, Friedman A H, Coleman R E, McLendon R E, Bigner S H, Zhao X G, Garcia-Turner A M, Pegram C N, Wikstrand C J, Shafman T D, Herndon 2nd  J E, Provenzale J M, Zalutsky M R, Bigner D D. Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.  J Clin Oncol. 2000;  18 3862-3672
• 9 De Santis R, Albertoni C, Petronzelli F, Campo S, D'Alessio V, Rosi A, Anastasi A M, Lindstedt R, Caroni N, Arseni B, Chiodi P, Verdoliva A, Cassani G, Chinol M, Paganelli G, Carminati P. Low and high tenascin-expressing tumors are efficiently targeted by ST2146 monoclonal antibody.  Clin Cancer Res. 2006;  12 (7 Pt 1) 2191-2196
• 10 Emrich J G, Brady L W, Quang T S, Class R, Miyamoto C, Black P, Rodeck U. Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment.  Am J Clin Oncol. 2002;  25 541-546
• 11 Goetz C, Rachinger W, Poepperl G, Decker M, Gildehaus F J, Stocker S, Jung G, Tatsch K, Tonn J C, Reulen H J. Intralesional radioimmunotherapy in the treatment of malignant glioma: clinical and experimental findings.  Acta Neurochir Suppl. 2003;  88 69-75
• 12 Goetz C M, Rachinger W, Decker M, Gildehaus F J, Stocker S, Jung G, Tatsch K, Tonn J C, Reulen H J. Distribution of labelled anti-tenascin antibodies and fragments after injection into intact or partly resected C6-gliomas in rats.  Cancer Immunol Immunother. 2005;  54 337-344
• 13 Grana C, Chinol M, Robertson C, Mazzetta C, Bartolomei M, De Cicco C, Fiorenza M, Gatti M, Caliceti P, Paganelli G. Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study.  Br J Cancer. 2002;  86 207-212
• 14 Hauck M L, Zalutsky M R. Enhanced tumour uptake of radiolabelled antibodies by hyperthermia: Part I: Timing of injection relative to hyperthermia.  Int J Hyperthermia. 2005;  21 1-11
• 15 Hauck M L, Zalutsky M R. Enhanced tumour uptake of radiolabelled antibodies by hyperthermia. Part II: Application of the thermal equivalency equation.  Int J Hyperthermia. 2005;  21 13-27
• 16 Hegi M E, Diserens A C, Gorlia T, Hamou M F, de Tribolet N, Weller M, Kros J M, Hainfellner J A, Mason W, Mariani L, Bromberg J E, Hau P, Mirimanoff R O, Cairncross J G, Janzer R C, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma.  N Engl J Med. 2005;  352 997-1003
• 17 Herold-Mende C, Mueller M M, Bonsanto M M, Schmitt H P, Kunze S, Steiner H H. Clinical impact and functional aspects of tenascin-C expression during glioma progression.  Int J Cancer. 2002;  98 362-369
• 18 Hopkins K, Papanastassiou V, Kemshead J T. The treatment of patients with recurrent malignant gliomas with intratumoral radioimmunoconjugates.  Recent Results Cancer Res. 1996;  141 159-175
• 19 Kim C H, Bak K H, Kim Y S, Kim J M, Ko Y, Oh S J, Kim K M, Hong E K. Expression of tenascin-C in astrocytic tumors: its relevance to proliferation and angiogenesis.  Surg Neurol. 2000;  54 235-240
• 20 Kleihues P, Cavenee W K. Tumors of the nervous system. Pathology and Genetics. IARC Press, Lyon, France 2000
• 21 Kneifel S, Cordier D, Good S, Ionescu M C, Ghaffari A, Hofer S, Kretzschmar M, Tolnay M, Apostolidis C, Waser B, Arnold M, Mueller-Brand J, Maecke H R, Reubi J C, Merlo A. Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-substance p.  Clin Cancer Res. 2006;  12 3843-3850
• 22 Lacroix M, Abi-Said D, Fourney D R, Gokaslan Z L, Shi W, DeMonte F, Lang F F, McCutcheon I E, Hassenbusch S J, Holland E, Hess K, Michael C, Miller D, Sawaya R. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival.  J Neurosurg. 2001;  95 190-198
• 23 Laperriere N, Zuraw L, Cairncross G. Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review.  Radiother Oncol. 2002;  64 259-273
• 24 Leins A, Riva P, Lindstedt R, Davidoff M S, Mehraein P, Weis S. Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma.  Cancer. 2003;  98 2430-2439
• 25 Lund-Johansen M, Bjerkvig R, Humphrey P A, Bigner S H, Bigner D D, Laerum O D. Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro.  Cancer Res. 1990;  50 6039-6044
• 26 Paganelli G, Grana C, Chinol M, Cremonesi M, De Cicco C, De Braud F, Robertson C, Zurrida S, Casadio C, Zoboli S, Siccardi A G, Veronesi U. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin.  Eur J Nucl Med. 1999;  26 348-357
• 27 Paganelli G, Bartolomei M, Ferrari M, Cremonesi M, Broggi G, Maira G, Sturiale C, Grana C, Prisco G, Gatti M, Caliceti P, Chinol M. Pre-targeted locoregional radioimmunotherapy with ⁹⁰Y-biotin in glioma patients: phase I study and preliminary therapeutic results.  Cancer Biother Radiopharm. 2001;  16 227-235
• 28 Paganelli G, Bartolomei M, Grana C, Ferrari M, Rocca P, Chinol M. Radioimmunotherapy of brain tumor.  Neurol Res. 2006;  28 518-522
• 29 Patel S J, Shapiro W R, Laske D W, Jensen R L, Asher A L, Wessels B W, Carpenter S P, Shan J S. Safety and feasibility of convection-enhanced delivery of Cotara for the treatment of malignant glioma: initial experience in 51 patients.  Neurosurgery. 2005;  56 1243-1252 , discussion 1252-1253
• 30 Petronzelli F, Pelliccia A, Anastasi A M, D'Alessio V, Albertoni C, Rosi A, Leoni B, De Angelis C, Paganelli G, Palombo G, Dani M, Carminati P, De Santis R. Improved tumor targeting by combined use of two antitenascin antibodies.  Clin Cancer Res. 2005;  11 (19 Pt 2) 7137s-7145s
• 31 Popperl G, Goldbrunner R, Gildehaus F J, Kreth F W, Tanner P, Holtmannspotter M, Tonn J C, Tatsch K. O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma.  Eur J Nucl Med Mol Imaging. 2005;  32 1018-1025
• 32 Quang T S, Brady L W. Radioimmunotherapy as a novel treatment regimen: ¹²⁵I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas.  Int J Radiat Oncol Biol Phys. 2004;  58 972-975
• 33 Reardon D A, Akabani G, Coleman R E, Friedman A H, Friedman H S, Herndon 2nd  J E, Cokgor I, McLendon R E, Pegram C N, Provenzale J M, Quinn J A, Rich J N, Regalado L V, Sampson J H, Shafman T D, Wikstrand C J, Wong T Z, Zhao X G, Zalutsky M R, Bigner D D. Phase II trial of murine (¹³¹)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas.  J Clin Oncol. 2002;  20 1389-1397
• 34 Reardon D A, Akabani G, Coleman R E, Friedman A H, Friedman H S, Herndon 2nd  J E, McLendon R E, Pegram C N, Provenzale J M, Quinn J A, Rich J N, Vredenburgh J J, Desjardins A, Gururangan S, Badruddoja M, Dowell J M, Wong T Z, Zhao X G, Zalutsky M R, Bigner D D. Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.  J Clin Oncol. 2006;  24 115-122
• 35 Reardon D A, Zalutsky M R, Bigner D D. Antitenascin-C monoclonal antibody radioimmunotherapy for malignant glioma patients.  Expert Rev Anticancer Ther. 2007;  7 675-687
• 36 Reardon D A, Zalutsky M R, Akabani G, Coleman R E, Friedman A H, Herndon 2nd  J E, McLendon R E, Pegram C N, Quinn J A, Rich J N, Vredenburgh J J, Desjardins A, Guruangan S, Boulton S, Raynor R H, Dowell J M, Wong T Z, Zhao X G, Friedman H S, Bigner D D. A pilot study: ¹³¹I-Antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost. Neuro Oncol 2008 Epub ahead of print: DOI: 10.1215/15228517-2007-053
• 37 Reist C J, Bigner D D, Zalutsky M R. Human IgG2 constant region enhances in vivo stability of anti-tenascin antibody 81C6 compared with its murine parent.  Clin Cancer Res. 1998;  4 2495-2502
• 38 Riva P, Arista A, Sturiale C, Moscatelli G, Tison V, Mariani M, Seccamani E, Lazzari S, Fagioli L, Franceschi G et al. Treatment of intracranial human glioblastoma by direct intratumoral administration of ¹³¹I-labelled anti-tenascin monoclonal antibody BC-2.  Int J Cancer. 1992;  51 7-13
• 39 Riva P, Franceschi G, Frattarelli M, Lazzari S, Riva N, Giuliani G, Casi M, Sarti G, Guiducci G, Giorgetti G, Gentile R, Santimaria M, Jermann E, Maeke H R. Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with ⁹⁰Y: a phase I study.  Clin Cancer Res. 1999;  5 (10 Suppl) 3275s-3280s
• 40 Riva P, Franceschi G, Frattarelli M, Riva N, Guiducci G, Cremonini A M, Giuliani G, Casi M, Gentile R, Jekunen A A, Kairemo K J. ¹³¹I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma - phase I and II study.  Acta Oncol. 1999;  38 351-359
• 41 Riva P, Franceschi G, Riva N, Casi M, Santimaria M, Adamo M. Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach.  Eur J Nucl Med. 2000;  27 601-609
• 42 Sasaki H, Yoshida K, Ikeda E, Asou H, Inaba M, Otani M, Kawase T. Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy.  Cancer. 1998;  82 1921-1931
• 43 Schold Jr S C, Zalutsky M R, Coleman R E, Glantz M J, Friedman A H, Jaszczak R J, Bigner S H, Bigner D D. Distribution and dosimetry of I-123-labeled monoclonal antibody 81C6 in patients with anaplastic glioma.  Invest Radiol. 1993;  28 488-496
• 44 Stummer W, Reulen H J, Novotny A, Stepp H, Tonn J C. Fluorescence-guided resections of malignant gliomas - an overview.  Acta Neurochir Suppl. 2003;  88 9-12
• 45 Stummer W, Pichlmeier U, Meinel T, Wiestler O D, Zanella F, Reulen H J. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.  Lancet Oncol. 2006;  7 392-401
• 46 Stupp R, Mason W P, van den Bent M J, Weller M, Fisher B, Taphoorn M J, Belanger K, Brandes A A, Marosi C, Bogdahn U, Curschmann J, Janzer R C, Ludwin S K, Gorlia T, Allgeier A, Lacombe D, Cairncross J G, Eisenhauer E, Mirimanoff R O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.  N Engl J Med. 2005;  352 987-996
• 47 Sunada H, Magun B E, Mendelsohn J, MacLeod C L. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation.  Proc Natl Acad Sci U S A. 1986;  83 3825-3829
• 48 Todaro L, Christiansen S, Varela M, Campodonico P, Pallotta M G, Lastiri J, Sacerdote de Lustig E, Bal de Kier Joffe E, Puricelli L. Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors.  J Neurooncol. 2007;  83 135-144
• 49 Tortosa A, Vinolas N, Villa S, Verger E, Gil J M, Brell M, Caral L, Pujol T, Acebes J J, Ribalta T, Ferrer I, Graus F. Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas.  Cancer. 2003;  97 1063-1071
• 50 Wikstrand C J, McLendon R E, Friedman A H, Bigner D D. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII.  Cancer Res. 1997;  57 4130-4140
• 51 Zalutsky M R, Moseley R P, Coakham H B, Coleman R E, Bigner D D. Pharmacokinetics and tumor localization of ¹³¹I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies.  Cancer Res. 1989;  49 2807-2813
• 52 Zalutsky M R, Moseley R P, Benjamin J C, Colapinto E V, Fuller G N, Coakham H P, Bigner D D. Monoclonal antibody and F(ab′)2 fragment delivery to tumor in patients with glioma: comparison of intracarotid and intravenous administration.  Cancer Res. 1990;  50 4105-4110
• 53 Zalutsky M R. Targeted radiotherapy of brain tumours.  Br J Cancer. 2004;  90 1469-1473
• 54 Zalutsky M R. Current status of therapy of solid tumors: brain tumor therapy.  J Nucl Med. 2005;  46 Suppl 1 151S-156S
• 55 Zalutsky M R, Reardon D A, Akabani G, Coleman R E, Friedman A H, Friedman H S, McLendon R E, Wong T Z, Bigner D D. Clinical experience with alpha-particle emitting ²¹¹At: treatment of recurrent brain tumor patients with ²¹¹At-labeled chimeric antitenascin monoclonal antibody 81C6.  J Nucl Med. 2008;  49 30-38