title: Selective uptake of p-borophenylalanine by undifferentiated thyroid carcinoma for boron neutron capture therapy.
abstract: Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10B-boronated compounds by some tumors, followed by irradiation with an appropriate neutron beam. The radioactive boron originated (11B) decays releasing 7Li, gamma rays and alpha particles, and these latter will destroy the tumor. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. In in vitro studies, the uptake of p-10borophenylalanine (BPA) by the UTC cell line ARO, primary cultures of normal bovine thyroid cells (BT), and human follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was observed between proliferating and quiescent ARO cells. The uptake by quiescent ARO, BT, and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5, respectively (p < 0.001). In in vivo studies, ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg body weight) was injected intraperitoneally. The animals were sacrificed between 30 and 150 minutes after the injection. With 350 mg, tumor uptake was highest after 60 minutes and the tumor/normal thyroid and tumor/blood ratios were 3 and 5, respectively. When 600 mg/kg body weight BPA were administered, after 90 minutes the tumor/blood, tumor/normal thyroid, and tumor/distal skin ratios for 10B concentrations per gram of tissue were approximately 3, showing a selective uptake by the tumor. The present experimental results open the possibility of applying BNCT for the treatment of UTC.
authors.affiliation: Division of Nuclear Biochemistry, Department of Radiobiology, National Atomic Energy Commission, Buenos Aires, Argentina.
authors.forename: M A
authors.initials: MA
authors.lastname: Dagrosa
authors.forename: M
authors.initials: M
authors.lastname: Viaggi
authors.forename: E
authors.initials: E
authors.lastname: Kreimann
authors.forename: S
authors.initials: S
authors.lastname: Farías
authors.forename: R
authors.initials: R
authors.lastname: Garavaglia
authors.forename: M
authors.initials: M
authors.lastname: Agote
authors.forename: R L
authors.initials: RL
authors.lastname: Cabrini
authors.forename: J L
authors.initials: JL
authors.lastname: Dadino
authors.forename: G J
authors.initials: GJ
authors.lastname: Juvenal
authors.forename: M A
authors.initials: MA
authors.lastname: Pisarev
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000818:Animals; D001895:Boron; D001896:Boron Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007554:Isotopes; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D014407:Tumor Cells, Cultured
chemical_list: D001896:Boron Compounds; D007554:Isotopes; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D001895:Boron; C033685:4-boronophenylalanine