Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with  213 Bi-substance P analogue

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Abstract

Background

Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. ²¹³Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures.

Material and methods

Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq ²¹³Bi- DOTA-[Thi ⁸,Met(O ₂) ¹¹]-substance P ( ²¹³Bi-DOTA-SP) in 2-month intervals. ⁶⁸Ga-DOTA-[Thi ⁸,Met(O ₂) ¹¹]-substance P ( ⁶⁸Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI.

Results

Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq ²¹³Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.

Conclusions

Targeted alpha therapy of secondary GBM with ²¹³Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.

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Author and article information

Contributors

Jolanta Kunikowska: +48 22 599 22 70 , jolanta.kunikowska@wum.edu.p

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur. J. Nucl. Med. Mol. Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 30 April 2018

Publication date PMC-release: 30 April 2018

Publication date (Print): 2018

Volume: 45

Issue: 9

Pages: 1636-1644

Affiliations

[1 ]ISNI 0000000113287408, GRID grid.13339.3b, Department of Nuclear Medicine, , Medical University of Warsaw, ; ul. Banacha 1 a, 02-097 Warsaw, Poland

[2 ]GRID grid.443865.8, European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, ; Karlsruhe, Germany

[3 ]ISNI 0000 0001 2237 2890, GRID grid.418955.4, Department of Neurosurgery, , Institute of Psychiatry and Neurology, ; Warsaw, Poland

[4 ]Department of Nuclear Medicine, Brodnowski Hospital, Warsaw, Poland

[5 ]ISNI 0000 0001 0941 0848, GRID grid.450295.f, Radioisotope Centre POLATOM, , National Centre for Nuclear Research, ; Otwock, Poland

[6 ]ISNI 0000 0004 0446 2659, GRID grid.135519.a, Nuclear and Radiochemistry Group, Nuclear Security and Isotope Technology Division, , Oak Ridge National Laboratory, ; Oak Ridge, TN 38731-6229 USA

[7 ]ISNI 0000 0001 1371 2275, GRID grid.418696.4, Department of Neurology, , Military Institute of Aviation Medicine, ; Warsaw, Poland

[8 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Neurosurgery, , Bern and University of Basel, ; Spitalgasse 32, Bern, Switzerland

Article

Publisher ID: 4015

DOI: 10.1007/s00259-018-4015-2

PMC ID: 6061489

PubMed ID: 29713762

SO-VID: 12134c32-39b6-4021-a0e6-ac89d37a9bd5

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 5 December 2017

Date accepted : 9 April 2018

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: glioblastoma,gbm,213bi-dota-sp,68ga-dota-sp,targeted alpha therapy,substance p

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: glioblastoma, gbm, 213bi-dota-sp, 68ga-dota-sp, targeted alpha therapy, substance p