Effects of l-DOPA pre-loading on the uptake of boronophenylalanine using the F98 glioma and B16 melanoma models.
The present study was undertaken to evaluate the effects of l-DOPA pre-loading on the uptake of BPA using the F98 rat glioma and the murine B16 melanoma models. In vitro pretreatments of F98 glioma and B16 melanoma cells with l-DOPA, followed by exposure to BPA increased boron uptake, as determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES). Based on this, in vivo studies were initiated in F98 glioma bearing rats. Initially, the l-DOPA dosing paradigm was evaluated. Maximum tumor boron uptake was observed following i.p. administration of l-DOPA (50mg/kg) followed 24h later by BPA (31.8±8.9 vs. 17.2±6.3µg/g for BPA alone). Next, the effect of l-DOPA pre-loading as a function of the route of administration of BPA was evaluated in F98 glioma bearing rats. The greatest increase in uptake was seen following i.v. administration of BPA, while in contrast no significant increase was seen following intracarotid (i.c.) administration (38.6±12.4 vs. 34.2±10.9). Cellular localization of the F98 glioma, as determined by secondary ion mass spectrometry (SIMS) boron imaging revealed equivalent tumor boron concentrations following l-DOPA pre-loading. In vivo studies in B16 melanoma bearing mice showed equivalent tumor boron values in treated and untreated mice, suggesting that the effects of l-DOPA pre-loading may depend both on the histologic type of tumor and its anatomic site.
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA.
Weilian
W
Yang
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA. Electronic address: rolf.barth@osumc.edu.
Rolf F
RF
Barth
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA.
Tianyao
T
Huo
University of Tennessee, Department of Chemistry, Knoxville, TN 37996, USA.
George W
GW
Kabalka
University of Tennessee, Department of Chemistry, Knoxville, TN 37996, USA.
Aarif L
AL
Shaikh
Cornell University, Department of Biomedical Engineering, Ithaca, NY 14853, USA.
Syed A
SA
Haider
Cornell University, Department of Biomedical Engineering, Ithaca, NY 14853, USA.
Subhash
S
Chandra
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D004357:Drug Synergism; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000532:radiotherapy; D007980:Levodopa / Q000008:administration & dosage*; D008545:Melanoma / Q000378:metabolism* / Q000532:radiotherapy; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011292:Premedication / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
D001896:Boron Compounds; D007980:Levodopa; D010649:Phenylalanine; C033685:4-boronophenylalanine
B16 murine melanoma; Boronophenylalanine; F98 rat glioma; SIMS; l-DOPA pre-loading