Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat gliomaReportar como inadecuado




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Radiation Oncology

, 12:26

Radiation Biology and Molecular Radiation Oncology

Abstract

BackgroundBoron neutron capture therapy BNCT is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate BSH derivative, 1-amino-3- fluorocyclobutane-1-carboxylic acid ACBC-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy BNCT of the F98 rat glioma.

MethodsWe evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine BPA, in vitro and in vivo, following intravenous i.v. administration and intratumoral i.t. convection-enhanced delivery CED in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA-i.v., BNCT with ACBC-BSH-CED, and BNCT concomitantly using BPA-i.v. and ACBC-BSH-CED.

ResultsIn vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery CED, ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH-CED group and BPA-i.v. group of rats. The tumor-brain boron-10 concentration ratio was higher with ACBC-BSH-CED than that of BPA-i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA-i.v. and ACBC-BSH-CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant.

ConclusionsOur findings suggest that further studies are warranted to evaluate ACBC-BSH-CED as a boron delivery agent.

KeywordsBoron neutron capture therapy F98 rat glioma model ACBC-BSH Abbreviations%ILSPercent increased lifespan

BBoron-10

ACBC1-amino-3- fluorocyclobutane-1-carboxylic acid

b.w.Body weight

BBBBlood-brain barrier

BNCTBoron neutron capture therapy

BPABoronophenylalanine

BSABovine serum albumin

BSHSodium borocaptate

CBECompound biological effectiveness

CEDConvection-enhanced delivery

DMEMDulbecco’s Modified Eagle Medium

HWNIFHeavy water neutron irradiation facility

i.c.intracarotid

i.t.intratumoral

i.v.intravenous

ICP-AESInductively coupled plasma atomic emission spectroscopy

ICRUInternational Commission on Radiation Units and Measurement

KURKyoto University Research Reactor Institute

LETLinear energy transfer

MeSTMedian survival time

MSTMean survival time

PBSPhosphate-buffered saline

PETPositron emission tomography

RBERelative biological effectiveness

SDStandard deviation

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Autor: Gen Futamura - Shinji Kawabata - Naosuke Nonoguchi - Ryo Hiramatsu - Taichiro Toho - Hiroki Tanaka - Shin-Ichiro Masunaga -

Fuente: https://link.springer.com/







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