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

  • Leszek Królicki
  • Frank Bruchertseifer
  • Jolanta KunikowskaEmail author
  • Henryk Koziara
  • Bartosz Królicki
  • Maciej Jakuciński
  • Dariusz Pawlak
  • Christos Apostolidis
  • Saed Mirzadeh
  • Rafał Rola
  • Adrian Merlo
  • Alfred Morgenstern
Original Article


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.


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.


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.


Glioblastoma multiforme GBM 213Bi-DOTA-SP 68Ga-DOTA-SP Targeted alpha therapy TAT Substance P 



At the EANM Congress in Gothenburg in 2014, this paper was among the 6 selected finalists for the Marie Curie Award.

The authors are indebted for the use of parts of the 225Ac/213Bi to the U.S. Department of Energy’s, Office of Nuclear Physics, Isotope Development and Production for Research and Applications Program.

We thank the Radiochemistry Group in the Department of Nuclear Medicine, the nursing staff and the nuclear medicine technologists of the Medical University of Warsaw for their support.

Compliance with ethical standards

This article does not contain any studies with animals performed by any of the authors.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

All authors declare that they have no conflict of interest in relation to this article.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Leszek Królicki
    • 1
  • Frank Bruchertseifer
    • 2
  • Jolanta Kunikowska
    • 1
    Email author
  • Henryk Koziara
    • 3
  • Bartosz Królicki
    • 3
  • Maciej Jakuciński
    • 4
  • Dariusz Pawlak
    • 5
  • Christos Apostolidis
    • 2
  • Saed Mirzadeh
    • 6
  • Rafał Rola
    • 7
  • Adrian Merlo
    • 8
  • Alfred Morgenstern
    • 2
  1. 1.Nuclear Medicine DepartmentMedical University of WarsawWarsawPoland
  2. 2.European Commission, Joint Research Centre, Directorate for Nuclear Safety and SecurityKarlsruheGermany
  3. 3.Department of NeurosurgeryInstitute of Psychiatry and NeurologyWarsawPoland
  4. 4.Department of Nuclear MedicineBrodnowski HospitalWarsawPoland
  5. 5.Radioisotope Centre POLATOMNational Centre for Nuclear ResearchOtwockPoland
  6. 6.Nuclear and Radiochemistry Group, Nuclear Security and Isotope Technology DivisionOak Ridge National LaboratoryOak RidgeUSA
  7. 7.Department of NeurologyMilitary Institute of Aviation MedicineWarsawPoland
  8. 8.NeurosurgeryBern and University of BaselBaselSwitzerland

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