Glioblastoma multiforme (GBM), primary brain tumor, is the most common and most malignant of the glia tumors. It is characterized by the worst prognosis with a median overall survival time of only 9–15 months. The infiltrating character of the tumor, its molecular heterogeneity, as well as the protective effects of the blood-brain barrier are the main causes for the insufficiency of established frontline treatments (surgery, radiotherapy, and chemotherapy).
The best treatment strategy for patients with recurrent GBM is unclear and controversial. Even with established state-of-the-art treatment in almost 90% of patients, the recurrence of disease is observed and median survival after recurrence is less than 6 months.
An alternative method of treatment is to apply the drug locally. It has been shown that GBM overexpresses the of NK-1 receptor and substance P (SP) can be used as a ligand. Alpha emitters, with shorter range and higher energy than beta emitters, offer the new potential for selective irradiation of tumors, with minimizing damage to adjacent tissue.
This chapter describes the use of radiolabeled SP for intratumoral treatment of the glia tumors.
Glioblastoma multiforme Targeted alpha therapy Substance P 213Bi 68Ga 225Ac
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The authors are indebted for use of parts of the 225Ac/213Bi to the US Department of Energy, Office of Nuclear Physics, Isotope Development and Production for Research and Applications Program.
Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83:588–93.CrossRefPubMedPubMedCentralGoogle Scholar
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;10:987–96.CrossRefGoogle Scholar
Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, North American Brain Tumor Consortium, et al. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro-Oncology. 2008;10:162–70.CrossRefPubMedPubMedCentralGoogle Scholar
Tatter SB. Recurrent malignant glioma in adults. Curr Treat Options in Oncol. 2002;3:509–24.CrossRefGoogle Scholar
Chang SM, Theodosopoulos P, Lamborn K, Malec M, Rabbitt J, Page M, Prados MD. Temozolomide in the treatment of recurrent malignant glioma. Cancer. 2004;100:605–11.CrossRefPubMedGoogle Scholar
Barbagallo GM, Jenkinson MD, Brodbelt AR. ‘Recurrent’ glioblastoma multiforme, when should we reoperate? Br J Neurosurg. 2008;22:452–5.CrossRefPubMedGoogle Scholar
Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, et al. Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol. 2010;28:3838–43.CrossRefPubMedPubMedCentralGoogle Scholar
Riva P, Arista A, Franceschi G, Frattarelli M, Sturiale C, Riva N, et al. Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors. Cancer Res. 1995;55:5952s–6s.PubMedGoogle Scholar
Merlo A, Hausmann O, Wasner M, Steiner P, Otte A, Jermann E. Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res. 1999;5:1025–33.PubMedGoogle Scholar
Bigner DD, Brown MT, Friedman AH, Coleman RE, Akabani G, Friedman HS, et al. Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results. J Clin Oncol. 1998;16:2202–12.CrossRefPubMedGoogle Scholar
Schumacher T, Hofer S, Eichhorn K, Wasner M, Zimmerer S, Freitag P, et al. 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. 2002;29:486–93.CrossRefPubMedGoogle Scholar
Kneifel S, Cordier D, Good S, Ionescu MC, Ghaffari A, Hofer S, et al. 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;12:3843–50.CrossRefPubMedGoogle Scholar
Sgouros G, Roeske JC, McDevitt MR, Palm S, Allen BJ, Fisher DR, et al. MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51(2):311–28.CrossRefPubMedPubMedCentralGoogle Scholar
Barendsen GW. Modification of radiation damage by fractionation of dose anoxia + chemical protectors in relation to LET. Ann N Y Acad Sci. 1964;114(1):96–114.CrossRefPubMedGoogle Scholar
Barendsen GW, Koot CJ, van Kerson GR, Bewley DK, Field SB, Parnell CJ. The effect of oxygen on the impairment of the proliferative capacity of human cells in culture by ionizing radiations of different LET. Int J Radiat Biol. 1966;10:317–27.Google Scholar
Wulbrand C, Seidl C, Gaertner FC, Bruchertseifer F, Morgenstern A, Essler M, Senekowitsch-Schmidtke R. Alpha-particle emitting (213)Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation. PLoS One. 2013;8(5):e64730.CrossRefPubMedPubMedCentralGoogle Scholar
Friesen C, Glatting G, Koop B, Schwarz K, Morgenstern A, Apostolidis C, et al. Breaking chemoresis- tance and radioresistance with [213Bi]anti-CD45 antibodies in leu- kemia cells. Cancer Res. 2007;67(5):1950–8.CrossRefPubMedGoogle Scholar
Hennig IM, Laissue JA, Horisberger U, Reubi JC. Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer. 1995;61:786–92.CrossRefPubMedGoogle Scholar
Cordier D, Forrer F, Bruchertseifer F, Morgenstern A, Apostolidis C, Good S, et al. Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging. 2010;37:1335–44.CrossRefPubMedGoogle Scholar
Cordier D, Forrer F, Kneifel S, Sailer M, Mariani L, et al. Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P: results from a phase I study. J Neuro-Oncol. 2010;100:129–36.CrossRefGoogle Scholar
Krolicki L, Morgenstern A, Kunikowska J, Koziara H, Królicki B, Jakuciński M, et al. Recurrent glioblastoma multiforme - local alpha emiters targeted therapy with 213Bi-DOTA-substance P. Eur J Nucl Med Mol Imaging. 2015;42:S84–5.Google Scholar
Krolicki L, Morgenstern A, Kunikowska J, Koziara H, Królicki B, Jakuciński M, et al. Secondary glioblastoma multiforme - local alpha emiters targeted therapy with Bi-213-DOTA-substance P. Eur J Nucl Med Mol Imaging. 2016;43:S158.Google Scholar