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Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 1994 Aug 30; Vol. 30 (1), pp. 105-15. - Publication Year :
- 1994
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Abstract
- Purpose: Gliomas, squamous carcinomas and different adenocarcinomas from breast, colon and prostate might have an increased number of epidermal growth factor (EGF) receptors. The receptors are, in these cases, candidates for binding of receptor specific toxic conjugates that might inactivate cellular proliferation. The purpose of this study was to evaluate whether it is reasonable to try ligand-dextran based conjugates for therapy.<br />Methods and Materials: EGF or TGF alpha were conjugated to dextran and binding, internalization, retention and degradation of eight types of such conjugates were analyzed in EGF-receptor amplified glioma cells. The conjugates were labelled with radioactive nuclides to allow detection and two of the conjugates were carrying boron in the form of carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests, applying 125I-EGF, were made with cultured breast, colon and prostate adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to label with 76Br for positron emission tomography and with 131I for radionuclide therapy were also made.<br />Results: The dextran part of the conjugates did not prevent receptor specific binding. The amount of receptor specific binding varied between the different types of conjugates and between the tested cell types. The dextran part improved intracellular retention and radioactive nuclides were retained for at least 20-24 h. The therapeutical effect improved when 131I was attached to EGF-dextran instead of native EGF.<br />Conclusion: The improved cellular retention of the ligand-dextran conjugates is an important property since it gives extended exposure time when radionuclides are applied and flexibility in the choice of time for application of neutrons in boron neutron capture therapy (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the applied neutron fields covers rather wide areas around the primary tumor, locally spread cells that otherwise would escape treatment to be inactivated.
- Subjects :
- Adenocarcinoma radiotherapy
Adenocarcinoma ultrastructure
Animals
Boron Compounds therapeutic use
Carcinoma radiotherapy
Carcinoma ultrastructure
Colonic Neoplasms radiotherapy
Colonic Neoplasms ultrastructure
Dextrans metabolism
Drug Carriers
Epidermal Growth Factor metabolism
ErbB Receptors metabolism
Glioma radiotherapy
Glioma ultrastructure
Humans
Iodine Radioisotopes
Male
Mammary Neoplasms, Experimental radiotherapy
Mammary Neoplasms, Experimental ultrastructure
Models, Biological
Neoplasms, Experimental radiotherapy
Neoplasms, Experimental ultrastructure
Prostatic Neoplasms radiotherapy
Prostatic Neoplasms ultrastructure
Rats
Rats, Sprague-Dawley
Transforming Growth Factor alpha metabolism
Tumor Cells, Cultured
Boron Neutron Capture Therapy methods
ErbB Receptors physiology
Neoplasms radiotherapy
Neoplasms ultrastructure
Subjects
Details
- Language :
- English
- ISSN :
- 0360-3016
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 7521866
- Full Text :
- https://doi.org/10.1016/0360-3016(94)90525-8