Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading.
One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.
CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome, Italy. silvia.capuani@roma1.infn.it
S
S
Capuani
T
T
Gili
M
M
Bozzali
S
S
Russo
P
P
Porcari
C
C
Cametti
M
M
Muolo
E
E
D'Amore
B
B
Maraviglia
G
G
Lazzarino
F S
FS
Pastore
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D066298:In Vitro Techniques; D007980:Levodopa / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D007980:Levodopa; D010649:Phenylalanine; C033685:4-boronophenylalanine