DOI: 10.1007/s00259-018-4015-2Pages: 1-9

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

1. Medical University of Warsaw, Department of Nuclear Medicine

2. European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security

3. Institute of Psychiatry and Neurology, Department of Neurosurgery

4. Brodnowski Hospital, Department of Nuclear Medicine

5. National Centre for Nuclear Research, Radioisotope Centre POLATOM

6. Oak Ridge National Laboratory, Nuclear and Radiochemistry Group, Nuclear Security and Isotope Technology Division

7. Military Institute of Aviation Medicine, Department of Neurology

8. Bern and University of Basel, Neurosurgery

Correspondence to:
Jolanta Kunikowska
Tel: +48 22 599 22 70
Email: jolanta.kunikowska@wum.edu.p

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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-[Thi8,Met(O2)11]-substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)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.

This article is freely available, click here to access the full text/PDF

  • Accepted: Apr 9, 2018
  • Online: Apr 30, 2018

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