[Boron neutron capture therapy applied to undifferentiated thyroid carcinoma].
Undifferentiated thyroid carcinoma (UTC) is an aggressive tumor with a poor prognosis due to the lack of an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of boron by the tumor and its activation by a neutron beam, releasing lithium-7 and an alpha particle that will kill the tumor cells by their high linear energy transfer (LET). In previous studies we have shown a selective uptake of borophenylalanine (10BPA) in a human UTC cell line (ARO) and in NIH nude mice implanted with this cell line. When these animals were injected with BPA and irradiated with an appropriated neutron beam, we observed a 100% of tumor growth control and a 50% of histological cure when the initial tumor volume was 50 mm3 or less. Further studies with BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha, beta-dihydroxyethyl)-deutero-porphyrin IX) showed that when this porphyrin was injected 5-7 days before BPA, and the animals were sacrificed 60 min after the i.p. injection of BPA, a significant increase in boron uptake by the tumor was found (45-38 ppm with both compounds vs. 20 ppm with BPA alone). The application of BNCT using the combination of boron compounds showed a 100% of complete remission in tumors with initial volumes under 50 mm3. Dogs suffer spontaneous UTC, with a similar biological behavior to the human tumor, and a selective uptake of BPA. These results open the possibility of applying BNCT to UTC.
Pisarev
Mario A
MA
Departamento de Radiobiología, Centro Atómico Constituyentes, Av. General Paz 1499,1650 San Martin, Buenos Aires, Argentina. pisarev@cnea.gov.ar
Dagrosa
Maria A
MA
Thomasz
Lisa
L
Juvenal
Guillermo
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use*; D001896:Boron Compounds / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D002277:Carcinoma / Q000532:radiotherapy*; D002330:Carmustine / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006801:Humans; D018499:Linear Energy Transfer / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011344:Procarbazine / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D014750:Vincristine / Q000627:therapeutic use
C507890:2,3,5,6-tetrafluoro-4-sulfanylbenzoic acid; C436045:4-dihydroxyborylphenylalanine; D001565:Benzoates; D001896:Boron Compounds; D013438:Sulfhydryl Compounds; D011344:Procarbazine; D010649:Phenylalanine; D014750:Vincristine; D002945:Cisplatin; D002330:Carmustine