title: Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.
abstract: OBJECTIVE
  Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis.
  
  
  METHODS
  The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples.
  
  
  RESULTS
  The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit).
  
  
  CONCLUSIONS
  We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Carpano
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Perona
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Nievas
authors.affiliation: Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Maria
authors.initials: M
authors.lastname: Olivera
authors.affiliation: Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín, Argentina.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Santa Cruz
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina; School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandizzi
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina; School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Romulo
authors.initials: R
authors.lastname: Cabrini
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina; National Research Council of Argentina, Buenos Aires, Argentina; Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mario
authors.initials: M
authors.lastname: Pisarev
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina; National Research Council of Argentina, Buenos Aires, Argentina.
authors.forename: Guillermo Juan
authors.initials: GJ
authors.lastname: Juvenal
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, San Martín, Argentina; National Research Council of Argentina, Buenos Aires, Argentina. Electronic address: dagrosa@cnea.gov.ar.
authors.forename: Maria Alejandra
authors.initials: MA
authors.lastname: Dagrosa
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001895:Boron / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D010649:Phenylalanine / Q000493:pharmacokinetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011868:Radioisotopes / Q000493:pharmacokinetics; D012878:Skin Neoplasms; D014018:Tissue Distribution; D047368:Tumor Burden; D000096142:Cutaneous Malignant Melanoma
chemical_list: D001896:Boron Compounds; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011868:Radioisotopes; D010649:Phenylalanine; D001895:Boron