L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy
- INFM-CNR CRS SOFT, Physics Department, 'Sapienza' University of Rome (Italy)
- Neuroimaging Laboratory, Santa Lucia Foundation, Rome (Italy)
- Department of Neurosurgery, Manchester University Hospital, Manchester (United Kingdom)
- Servizio Qualita'e Sieurezza della Sperimentazione Animale, Istituto Superiore di Sanita, Rome (Italy)
- Department of Biological Science, University 'Rome III', Rome (Italy)
- Enrico Fermi Center, Rome (Italy)
- Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Catania (Italy)
- Department of Neurosurgery, University 'Tor Vergata', Rome (Italy)
Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on {sup 10}B(n,{alpha}){sup 7}Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for {sup 10}B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.
- OSTI ID:
- 21124485
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 72, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2008.06.1493; PII: S0360-3016(08)02503-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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