INFINA (EX INFIP)   05545
INSTITUTO DE FISICA INTERDISCIPLINARIA Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
In vivo study of electroporation to optimize boron targeting in Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model
Autor/es:
N. OLAIZ; GARABALINO MA; POZZI ECC; THORP S; CUROTTO P; ITOIZ ME; AROMANDO R ; PORTU A; SAINT MARTIN G; MONTI HUGHES A; MARSHALL G; TRIVILLIN V A; SCHWINT AE
Lugar:
Pavia
Reunión:
Simposio; 8th Young Researchers BNCT Meeting; 2015
Resumen:
p { margin-bottom: 0in; direction: ltr; color: rgb(0, 0, 0); line-height: 200%; text-align: justify; widows: 2; orphans: 2; }p.western { font-family: "Times New Roman",serif; font-size: 12pt; }p.cjk { font-family: "Times New Roman",serif; font-size: 12pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 12pt; font-weight: bold; }a:link { color: rgb(0, 0, 255); }Introduction:The biodistribution of boron carriers in tumor in terms of absoluteand relative 10Bconcentration, retention in tumor, targeting homogeneity andmicrodistribution conditions the therapeutic efficacy of BNCT [1,2].Aim:To optimize the conditions of electroporation (EP) in the hamstercheek pouch oral cancer model and evaluate if EP can be used as anon-specific drug delivery system to optimize the delivery of theboron compounds p-Borophenylalanine(BPA) and sodium decahydro-decaborate (GB-10), improving thetherapeutic efficacy of BNCT. Materialsand methods:Exophytic tumors (Squamous Cell Carcinoma) were induced in the pouchof hamsters by topical application of dimethyl-benzanthracene. Weperformed electroporation experiments in tumors (1000 v/cm, 8 pulsesof 100µs) employing BPA or GB-10, varying the time between EP andthe 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=3hs); 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 [3]; 10.Control BPA-BNCT[3]; 11.Control GB-10-BNCT. The neutron irradiations were performed at thethermal facility of the RA-3 Nuclear Reactor. The animals werefollowed during 1 monthto assess clinicalsigns, tumor response and mucositis in dose-limiting precanceroustissue. Results:Based on tumor response, we calculated an index of effective EP thatoptimizes effective tumor response: 0.012-0.055 S/cm. Protocols 1, 2and 3 exhibited a high incidence of severe mucositis (grades 4 and 5)that precluded the evaluation of tumor response. Protocols 5 and 6(GB-10 BNCT + EP) improved tumor response vs protocol 11(GB-10-BNCT), with only mild-moderate mucositis (≤grade 3). Inparticular, for protocol 6 vs protocol 11, we observed an increase incomplete remissions in the case of small tumors (<10mm3),71% vs 7%, and in the case of medium tumors (10-100 mm3),25% vs 6%. Conclusion:We established the optimum conditions of EP invivo in the hamstercheek pouch oral cancer model and provided evidence that EP could bea tool to improve the therapeutic efficacy of BNCT invivo.