title: L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.
abstract: OBJECTIVE
  Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for (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
  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.
authors.affiliation: Physics Department, Sapienza University of Rome, Italy; Enrico Fermi Center, Rome, Italy. silvia.capuani@roma1.infn.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Capuani
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gili
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.forename: Salvatore
authors.initials: S
authors.lastname: Russo
authors.forename: Paola
authors.initials: P
authors.lastname: Porcari
authors.forename: Cesare
authors.initials: C
authors.lastname: Cametti
authors.forename: Emanuela
authors.initials: E
authors.lastname: D'Amore
authors.forename: Marco
authors.initials: M
authors.lastname: Colasanti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Venturini
authors.forename: Bruno
authors.initials: B
authors.lastname: Maraviglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lazzarino
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Pastore
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000097:blood / Q000378:metabolism* / Q000532:radiotherapy; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000494:pharmacology; D005910:Glioma / Q000097:blood / Q000378:metabolism* / Q000532:radiotherapy; D007980:Levodopa / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats
chemical_list: C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D015259:Dopamine Agents; D007980:Levodopa; D010649:Phenylalanine