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Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas.
- Source :
-
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine [Appl Radiat Isot] 2004 Nov; Vol. 61 (5), pp. 981-5. - Publication Year :
- 2004
-
Abstract
- 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 (125)I-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 microg/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.
- Subjects :
- Animals
Boron Compounds pharmacokinetics
Brain Neoplasms genetics
Cell Line, Tumor
Epidermal Growth Factor pharmacokinetics
ErbB Receptors genetics
Glioma genetics
Humans
Injections, Intravenous
Phenylalanine administration & dosage
Phenylalanine pharmacokinetics
Radiotherapy Dosage
Rats
Rats, Inbred F344
Recombinant Proteins administration & dosage
Recombinant Proteins pharmacokinetics
Tissue Distribution
Transfection
Boron Compounds administration & dosage
Boron Neutron Capture Therapy methods
Brain Neoplasms metabolism
Brain Neoplasms radiotherapy
Epidermal Growth Factor administration & dosage
ErbB Receptors metabolism
Glioma metabolism
Glioma radiotherapy
Phenylalanine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0969-8043
- Volume :
- 61
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
- Publication Type :
- Academic Journal
- Accession number :
- 15308179
- Full Text :
- https://doi.org/10.1016/j.apradiso.2004.05.071