Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 37, Issue 7, pp 1335-1344

First online:

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial

  • D. CordierAffiliated withDivision of Neurosurgery, University Hospitals Email author 
  • , F. ForrerAffiliated withInstitute of Nuclear Medicine, University Hospitals
  • , F. BruchertseiferAffiliated withEuropean Commission, Joint Research Centre, Institute for Transuranium Elements
  • , A. MorgensternAffiliated withEuropean Commission, Joint Research Centre, Institute for Transuranium Elements
  • , C. ApostolidisAffiliated withEuropean Commission, Joint Research Centre, Institute for Transuranium Elements
  • , S. GoodAffiliated withInstitute of Nuclear Medicine, University Hospitals
  • , J. Müller-BrandAffiliated withInstitute of Nuclear Medicine, University Hospitals
  • , H. MäckeAffiliated withInstitute of Nuclear Medicine, University HospitalsNuclear Medicine and Radiological Chemistry, University Hospital Basel
  • , J. C. ReubiAffiliated withInstitute of Pathology, University of Berne
    • , A. MerloAffiliated withDivision of Neurosurgery, University Hospitals

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Abstract

Purpose

Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting 90Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of 90Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide 213Bi with a mean tissue range of 81 µm may have a more favourable toxicity profile. Therefore, we evaluated locally injected 213Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality.

Methods

In a pilot study, we included five patients with critically located gliomas (WHO grades II–IV). After diagnosis by biopsy, 213Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated.

Results

Targeted radiopeptide therapy using 213Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. 213Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection.

Conclusion

This study provides proof of concept that targeted local radiotherapy using 213Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis.

Keywords

Glioma Substance P Targeted therapy 213Bi