Boron neutron capture therapy for undifferentiated thyroid carcinoma: preliminary results with the combined use of BPA and BOPP.
We have shown the selective uptake of borophenylalanine (BPA) by undifferentiated human thyroid cancer (UTC) ARO cells both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 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 (38-45 ppm with both compounds vs. 20 ppm with BPA alone). Five days post the i.p BOPP injection and 1h after BPA the ratios were: tumor/blood 3.75; tumor/distal skin 2. Other important ratios were tumor/thyroid 6.65 and tumor/lung 3.8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy).
Department of Radiobiology, Constituyentes Atomic Center, Av del Libertador 8250, 1429 Buenos Aires, Argentina. viaggi@cnea.gov.ar
M
M
Viaggi
M A
MA
Dagrosa
J
J
Longhino
H
H
Blaumann
O
O
Calzetta
S B
SB
Kahl
G J
GJ
Juvenal
M A
MA
Pisarev
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D003905:Deuteroporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D000098851:Carboranes
D001896:Boron Compounds; D003905:Deuteroporphyrins; D010649:Phenylalanine; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes; C436045:4-dihydroxyborylphenylalanine