Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas

• Published in: Applied radiation and isotopes 2004-11, Vol.61 (5), p.981-985
• Main Authors: Yang, Weilian, Barth, Rolf F, Wu, Gong, Bandyopadhyaya, Achintya K, Thirumamagal, B.T.S, Tjarks, Werner, Binns, Peter J, Riley, Kent, Patel, Hemant, Coderre, Jeffrey A, Ciesielski, Michael J, Fenstermaker, Robert A
• Format: Article
• Language: English
• Subjects: Animals; Boron Compounds - administration & dosage; Boron Compounds - pharmacokinetics; Boron neutron capture therapy; Boron Neutron Capture Therapy - methods; Boronated EGF; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Cell Line, Tumor; Convection enhanced delivery; Epidermal Growth Factor - administration & dosage; Epidermal Growth Factor - pharmacokinetics; F98 EGFR glioma; Glioma - genetics; Glioma - metabolism; Glioma - radiotherapy; Humans; Injections, Intravenous; Phenylalanine - administration & dosage; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacokinetics; Radiotherapy Dosage; Rats; Rats, Inbred F344; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacokinetics; Tissue Distribution; Transfection
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2004.05.071

The purpose of the present study was to further evaluate a boronated dendrimer (BD)-epidermal growth factor bioconjugate (BD-EGF), administered by means of convection enhanced delivery (CED), as a molecular targeting agent for boron neutron capture therapy (BNCT) of the F98 EGFR glioma. Twenty-four hours following CED of 125I-labeled BD-EGF 47.4% of the injected dose (ID) was retained in F98 EGFR gliomas compared to 12.3% in F98 WT (wildtype) receptor negative tumors. Normal brain values were in the range of 5.9–10.1% ID in the tumor bearing cerebral hemisphere. Boron concentrations in F98 EGFR gliomas were 22.3 and 11.7 μg/g following CED and i.t. injection, respectively. Based on these results, BNCT studies were initiated at the Massachusetts Institute of Technology nuclear reactor (MITRII). The mean survival time (MST) of rats that received BD-EGF either alone or in combination with boronophenylalanine (BPA), injected i.v., were 53±13 d and >61±14 d, respectively, compared to 40±5 d for BPA alone and 31±4 d for irradiated controls. These data show that CED improved the radiobiological effectiveness of BD-EGF and lay the groundwork for future studies using combinations of boron delivery agents for NCT of EGFR(+) gliomas.