Ongoing translational studies of therapeutic efficacy of BNCT/GB-10 and BNCT/GB-10+Electroporation for oral cancer in the RA-1 facility

SANTA CRUZ IS; PALMIERI MA; OLAIZ N; RAMOS PS; CASTILLO J; SCOLARI H; BARBERIS C; MONTI HUGHES A; POZZI EC; TRIVILLIN VA; MARSHALL G; SCHWINT AE; GARABALINO MA

Congreso; 10th YBNCT; 2019

Introduction: To explore the therapeutic potential of boron carriers and administrationprotocols for head and neck cancer in the hamster cheek pouch oral cancer model, weevaluated novel BNCT strategies employing boron compounds approved for their use inhumans (eg. Trivillin et al., 2006; Garabalino & Olaiz et al., 2019). Our previous studies inthe facility of the RA-1 Nuclear Reactor consisted in BPA/BNCT experiments on non-cancerized Syrian hamsters. RA-1 is of particular interest because it is located in BuenosAires and has a neutron spectrum that includes a fast neutron component that mightcontribute to the treatment of Squamous Cell Carcinomas. We also demonstrated thefeasibility of treating spontaneous head and neck tumors in domestic felines with BNCT inRA-1 and RA-6 Reactors (eg. Rao et al., 2004; Trivillin et al. 2008). Aim: performexperiments to assess the therapeutic efficacy of BNCT and radiotoxicity in vivo in an oralcancer model in the hamster cheek pouch using BNCT/GB-10 and the combination ofBNCT/GB-10 + Electroporation (EP) at the facility thermal RA-1. Materials andmethods: Tumors were induced in the right cheek pouch of Syrian hamsters as previously(Garabalino & Olaiz et al., 2019). Once the exophytic tumors developed, i.e. squamous cellcarcinomas, the animals were used for pilot BNCT studies: Group 1) BNCT/GB-10 (50 mg10 B/kg, iv) (n=17 tumors) and Group 2) BNCT/GB-10 (50 mg 10 B/kg, iv) +EP (10 min.post-administration of GB-10) (n=8 tumors). Electroporation was performed on each tumoremploying the standard sequence of pulses for electrochemotherapy (1000 v/cm, 8 pulsesof 100 μs). Prior to each in vivo BNCT study the volume of each tumor was determined.We arbitrarily defined 2 tumor volume ranges, i.e. small (1 mm 3 >volume >10 mm 3 ) andmedium/large (volume 10 mm 3 ). Irradiations were carried out 3 hours post-administrationof GB-10 in the RA-1 facility with 10 minutes exposures and using a 6 Li carbonateshielding. Tumor response and mucositis in precancerous tissue surrounding tumors wereevaluated 7, 10, 14, 21 and 28 days post-irradiation. All experiments were approved byCICUAL-CNEA. Results: No severe radiotoxicity (mucositis) was observed in theBNCT/GB-10 or BNCT/GB-10+EP protocols at any follow-up time. 28 days post-irradiation total tumor response (complete remission + partial remission) was 65% forBNCT/GB-10 and 88% for BNCT/GB-10+EP. Although these results are preliminary,small tumors´ overall response was increased in BNCT/GB-10+EP vs. BNCT/GB-10(100% vs 65%, respectively). For the case of medium and large tumors a total tumorresponse of 67% was obtained for both protocols. Conclusion: These preliminary datasuggest that BNCT/GB-10-and BNCT/GB-10+EP carried out at the RA-1 facility might betherapeutically useful for the treatment of head and neck tumors without associatedapparent radiotoxicity.