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Title: Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

Abstract

Purpose: 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 ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: 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{sup 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 {sup 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 correlationmore » between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 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{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.« less

Authors:
; ;  [1]; ; ;  [2]; ;  [1];  [3];  [1];  [3];  [3];  [1];  [3];  [1];  [3]
  1. Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina)
  2. Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín (Argentina)
  3. (Argentina)
Publication Date:
OSTI Identifier:
22458781
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 93; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOMEDICAL RADIOGRAPHY; BLOOD; BORON; BORON 10; CONCENTRATION RATIO; CORRELATIONS; DIAGNOSIS; INJECTION; MELANOMAS; MICE; NEUTRON CAPTURE THERAPY; PATIENTS; SCREENING; UPTAKE; VIABILITY

Citation Formats

Carpano, Marina, Perona, Marina, Rodriguez, Carla, Nievas, Susana, Olivera, Maria, Santa Cruz, Gustavo A., Brandizzi, Daniel, Cabrini, Romulo, School of Dentistry, University of Buenos Aires, Buenos Aires, Pisarev, Mario, National Research Council of Argentina, Buenos Aires, Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Juvenal, Guillermo Juan, National Research Council of Argentina, Buenos Aires, Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar, and National Research Council of Argentina, Buenos Aires. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2015.05.039.
Carpano, Marina, Perona, Marina, Rodriguez, Carla, Nievas, Susana, Olivera, Maria, Santa Cruz, Gustavo A., Brandizzi, Daniel, Cabrini, Romulo, School of Dentistry, University of Buenos Aires, Buenos Aires, Pisarev, Mario, National Research Council of Argentina, Buenos Aires, Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Juvenal, Guillermo Juan, National Research Council of Argentina, Buenos Aires, Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar, & National Research Council of Argentina, Buenos Aires. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment. United States. doi:10.1016/J.IJROBP.2015.05.039.
Carpano, Marina, Perona, Marina, Rodriguez, Carla, Nievas, Susana, Olivera, Maria, Santa Cruz, Gustavo A., Brandizzi, Daniel, Cabrini, Romulo, School of Dentistry, University of Buenos Aires, Buenos Aires, Pisarev, Mario, National Research Council of Argentina, Buenos Aires, Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Juvenal, Guillermo Juan, National Research Council of Argentina, Buenos Aires, Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar, and National Research Council of Argentina, Buenos Aires. Thu . "Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment". United States. doi:10.1016/J.IJROBP.2015.05.039.
@article{osti_22458781,
title = {Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment},
author = {Carpano, Marina and Perona, Marina and Rodriguez, Carla and Nievas, Susana and Olivera, Maria and Santa Cruz, Gustavo A. and Brandizzi, Daniel and Cabrini, Romulo and School of Dentistry, University of Buenos Aires, Buenos Aires and Pisarev, Mario and National Research Council of Argentina, Buenos Aires and Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires and Juvenal, Guillermo Juan and National Research Council of Argentina, Buenos Aires and Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar and National Research Council of Argentina, Buenos Aires},
abstractNote = {Purpose: 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 ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: 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{sup 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 {sup 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{sup 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{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.},
doi = {10.1016/J.IJROBP.2015.05.039},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 93,
place = {United States},
year = {2015},
month = {10}
}