Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial.
OBJECTIVE
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 (90)Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of (90)Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide (213)Bi with a mean tissue range of 81 microm may have a more favourable toxicity profile. Therefore, we evaluated locally injected (213)Bi-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, (213)Bi-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 (213)Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. (213)Bi-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.


CONCLUSIONS
This study provides proof of concept that targeted local radiotherapy using (213)Bi-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.
Division of Neurosurgery, University Hospitals, Basel, Switzerland. cordierd@uhbs.ch
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D
Cordier
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Forrer
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F
Bruchertseifer
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Morgenstern
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Apostolidis
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Good
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Müller-Brand
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Mäcke
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JC
Reubi
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Merlo
D000328:Adult; D000512:Alpha Particles / Q000627:therapeutic use*; D005240:Feasibility Studies; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007267:Injections; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010865:Pilot Projects; D013373:Substance P / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; C552249:substance P, 213Bi-DOTA(thienylalanyl(8)-methionyl(O2)(11))-; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D013373:Substance P