Experimental Studies of Boronophenylalanine ((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 ((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(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).

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.

• Authors: Marina Carpano, Marina Perona, Carla Rodriguez, Susana Nievas, Maria Olivera, Gustavo A Santa Cruz, Daniel Brandizzi, Romulo Cabrini, Mario Pisarev, Guillermo Juan Juvenal, Maria Alejandra Dagrosa
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 93 Issue 2 Pg. 344-52 (Oct 01 2015) ISSN: 1879-355X [Electronic] United States
• PMID: 26232853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Boron Compounds
• Ki-67 Antigen
• Platelet Endothelial Cell Adhesion Molecule-1
• Radioisotopes
• Phenylalanine
• Boron

Topics

• Animals
• Body Temperature (physiology)
• Boron (pharmacokinetics)
• Boron Compounds (pharmacokinetics)
• Boron Neutron Capture Therapy
• Cell Line, Tumor
• Humans
• Ki-67 Antigen (analysis)
• Melanoma (metabolism, pathology, radiotherapy)
• Mice
• Mice, Nude
• Phenylalanine (pharmacokinetics)
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis)
• Radioisotopes (pharmacokinetics)
• Skin Neoplasms
• Tissue Distribution
• Tumor Burden