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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2019

01-03-2019 | Original Article

Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma

Authors: Leszek Królicki, Frank Bruchertseifer, Jolanta Kunikowska, Henryk Koziara, Bartosz Królicki, Maciej Jakuciński, Dariusz Pawlak, Christos Apostolidis, Saed Mirzadeh, Rafał Rola, Adrian Merlo, Alfred Morgenstern

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2019

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Abstract

Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter 213Bi allows for selective irradiation and killing of tumor cells.

Material and methods

Twenty patients with recurrent GBM were included into the study following a standard therapy. 1–2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1–7 doses of 213Bi-DOTA-Substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-Substance P (68Ga-DOTA-SP) was co-injected with 213Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging.

Results

Treatment with activity up to 11.2 GBq 213Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of 213Bi-DOTA-SP was 7.5 months.

Conclusions

Treatment of recurrent GBM with 213Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity 225Ac/213Bi radionuclide generators is secured, targeted alpha therapy with 213Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.
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Metadata
Title
Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma
Authors
Leszek Królicki
Frank Bruchertseifer
Jolanta Kunikowska
Henryk Koziara
Bartosz Królicki
Maciej Jakuciński
Dariusz Pawlak
Christos Apostolidis
Saed Mirzadeh
Rafał Rola
Adrian Merlo
Alfred Morgenstern
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4225-7

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