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Locoregional Treatment of Glioblastoma With Targeted α Therapy: [213Bi]Bi-DOTA–Substance P Versus [225Ac]Ac-DOTA–Substance P—Analysis of Influence Parameters

Journal Article · · Clinical Nuclear Medicine
 [1];  [1];  [2];  [1];  [3];  [4];  [5];  [2];  [6]
  1. Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland
  2. European Commission, Joint Research Centre, Karlsruhe, Germany
  3. Radioisotope Centre POLATOM, National Centre for Nuclear Research, Otwock
  4. Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw
  5. Department of Neurology, Military Institute of Aviation Medicine, Warsaw, Poland
  6. Neurosurgical Center Berne and University of Basel, Switzerland.
+ Show Author Affiliations
Background

Glioblastoma (GB) is the most malignant primary brain tumor. Therefore, introduction of new treatment options is critically important. The aim of this study was to assess local treatment with α emitters [213Bi]Bi-DOTA–substance P (SP) and [225Ac]Ac-DOTA-SP.

Methods

Treatment was performed as salvage therapy in patients with recurrent primary and secondary GB. [213Bi]Bi-DOTA-SP with injected activity 1.85 GBq per cycle was used in 20 primary (48.2 ± 11.8 years old) and in 9 secondary (38.8 ± 10.8 years old) GB patients and [225Ac]Ac-DOTA-SP in 15 primary (45.1 ± 9.9 years old) and in 6 secondary (37.8 ± 6.4 years old) GB patients with a dose escalation scheme (10, 20, and 30 MBq).

Results

Local treatment with [213Bi]Bi-DOTA-SP and [225Ac]Ac-DOTA-SP was well tolerated with only few adverse effects. There was no statistically significant difference between [213Bi]Bi-DOTA-SP and [225Ac]Ac-DOTA-SP groups in survival parameters. For primary GB, survival parameters of patients treated with [213Bi]Bi-DOTA-SP and [225Ac]Ac-DOTA-SP were as follows(in months): progression-free survival time, 2.7 versus 2.4; OS-d (overall survival from time of diagnosis to death from any cause), 23.6 versus 21.0; OS-t (overall survival from the start of treatment to death from any cause), 7.5 versus 5.0; and OS-r (overall survival from recurrence in primary tumors to death from any cause), 10.9 versus 12.0. Survival parameters of secondary GB patients treated with [213Bi]Bi-DOTA-SP and [225Ac]Ac-DOTA-SP were as follows (in months): progression-free survival time, 5.8 versus 2.4; OS-d, 52.3 versus 65.0; OS-t, 16.4 versus 16.0; and OS-c (overall survival from conversion into secondary GB multiforme to death from any cause), 18.4 versus 36.0.

Conclusions

The similarity results of213Bi or225Ac may suggest that the local treatment of brain tumors can be greatly simplified. The experience to date shows that local radioisotope treatment of brain tumors requires further dosimetry studies, taking into account the complexity of biological processes.

Research Organization:
US Department of Energy (USDOE), Washington, DC (United States). Office of Science, Nuclear Physics (NP)
Sponsoring Organization:
USDOE
OSTI ID:
2424954
Journal Information:
Clinical Nuclear Medicine, Journal Name: Clinical Nuclear Medicine Journal Issue: 5 Vol. 48; ISSN 0363-9762
Publisher:
Wolters Kluwer Health
Country of Publication:
United States
Language:
English

References (14)

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‘Recurrent’ glioblastoma multiforme, when should we reoperate? journal January 2008
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The Added Value of Apparent Diffusion Coefficient to Cerebral Blood Volume in the Preoperative Grading of Diffuse Gliomas journal December 2011
225Ac- and 213Bi-Substance P Analogues for Glioma Therapy journal March 2020
Standards of care for treatment of recurrent glioblastoma—are we there yet? journal November 2012
Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma journal November 2018
Diffusion in Brain Extracellular Space journal October 2008
Production of Ac-225 from Th-229 for Targeted α Therapy journal October 2005
Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma – safety and efficacy journal April 2021
Intracavitary radioimmunotherapy of high-grade gliomas: present status and future developments journal April 2019
Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with 213Bi-substance P analogue journal April 2018
Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery journal January 2019
Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes journal June 2012

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