INFINA (EX INFIP)   05545
INSTITUTO DE FISICA INTERDISCIPLINARIA Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ELECTROPORACIÓN PARA OPTIMIZAR EL ?TARGETING? DE BORO EN LA TERAPIA POR CAPTURA NEUTRÓNICA EN BORO (BNCT): DESARROLLO E IMPLEMENTACIÓN DE LA TÉCNICA EN UN MODELO DE CÁNCER BUCAL EN HAMSTER
Autor/es:
N OLAIZ; GARABALINO M A; POZZI ECC; THORP S; CUROTTO P; ITOIZ M E; AROMANDO R; PORTU A; SAINT MARTIN G; MONTI HUGHES A; TRIVILLIN V A; MARSHALL G; SCHWINT A E
Lugar:
CABA
Reunión:
Congreso; Reunión Anual AATN 2014; 2014
Institución organizadora:
Comisión Nacional de Energía Atómica
Resumen:
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BNCT
is based on the capture reaction between 10B
localized preferentially in tumor, and thermal neutrons, generating
short range lethal particles that damage tumor, preserving healthy
tissue. The biodistribution of boron carriers in tumor in terms of
absolute and relative 10B
concentration, retention in tumor, targeting homogeneity and
microdistribution conditions the therapeutic efficacy of BNCT. It is
of great
relevance to optimize
the biodistribution of boron compounds authorized for their use in
humans, thus bridging the gap between research and clinical
application. Within this context, the aim of this study was to
optimize the conditions of electroporation (EP) in the hamster cheek
pouch oral cancer model and evaluate if EP can be used as a
non-specific drug delivery system to optimize the delivery of the
boron compounds p-Boro-phenyl-alanine
(BPA) and sodium decahydro-decaborate (GB-10), improving the
therapeutic efficacy of BNCT. Materials
and methods: Exophytic
tumors (Squamous Cell Carcinoma) were induced in the pouch of 30
Syrian hamsters by topical application of the carcinogen
dimethyl-benzanthracene (DMBA) twice a week for 3 months. We
performed electroporation experiments in tumors (1000 v/cm, 8 pulses
of 100µs) as part of 9 protocols employing BPA (15.5 mg 10B/kg
iv) or GB-10 (50 mg 10B/kg
iv), varying the time between EP and the administration of the boron
compound: (1) BPA (t=0 min) - EP (t=10 min) - irradiation (t=20 min);
(2) BPA (t=0 min) - EP (t=10 min) ? EP (2:50 hs) - irradiation (t=3
hs); (3) BPA (t=0 min) ? EP (2:50 hs) - irradiation (t=3 hs); (4)
BPA (t=0 min) ? EP (t=10 min) - irradiation (t=3 hs); (5) GB-10
(t=0 min) ? EP (2:50 hs) - irradiation (t=3 hs); (6) GB-10 (t=0
min) - EP (t=10 min) - irradiation (t=3 hs); (7) Control EP only; (8)
EP (t=0 min) - irradiation (t=2:50 hs); (9) Control beam only; (10)
Control BPA-BNCT (Molinari et al., 2012); (11) Control GB-10-BNCT
(Trivillin et al., 2004). The neutron irradiations were performed at
the thermal facility of the RA-3 Nuclear Reactor, 3 hours
post-administration of the boron compound, at a thermal neutron
fluence of 1.9 x 1012
n/cm2.
We evaluated the clinical signs of the animals, tumor response and
mucositis in precancerous tissue surrounding the treated tumors 7,
14, 21 and 28 days post-irradiation. Results:
A retrospective analysis of the EP conditions revealed that the
experiments were performed at 0.0055-0.055 S/cm. The detailed
analysis of the tumor response data and the calculation of an index
of effective EP revealed the EP window that optimizes effective tumor
response: 0.012-0.055 S/cm. Protocols 1, 2 and 3 exhibited a high
incidence of severe mucositis (grade 4 and 5) that precluded the
evaluation of tumor response. EP showed a therapeutic benefit in the
case of protocol 6 in terms of improved tumor control associated to
mild-moderate mucositis in precancerous tissue (≤grade
3). Comparing the data of tumor control corresponding to protocol 6
with those corresponding to protocol 11 (GB-10-BNCT reported in
Trivillin et al., 2004), we observed an increase in complete
remissions in the case of small tumors (<10mm3),
71% vs 42%, and in the case of medium tumors (10-100 mm3),
43% vs 7%. Conclusion:
We established the optimum conditions of EP in
vivo in the hamster cheek
pouch oral cancer model and provided evidence that EP could be a tool
to improve the therapeutic efficacy of BNCT in
vivo, employing boron
compounds approved for their use in humans.