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Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth
J Carlsson1, L Gedda, C Grönvik
1Department of Radiation Sciences, Akademiska Hospital, Uppsala University, Sweden.
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.
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.
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.
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.
Insights
Ligand-dextran conjugates show promise for cancer therapy by improving retention of radioactive agents in tumor cells. This approach may enhance the effectiveness of treatments like boron neutron capture therapy (BNCT).
Area of Science:
- Oncology
- Bioconjugation Chemistry
- Radiopharmaceutical Development
Background:
- Certain cancers, including gliomas and adenocarcinomas, overexpress epidermal growth factor (EGF) receptors.
- Targeting these EGF receptors with specific conjugates offers a potential strategy to inhibit cancer cell proliferation.
- Ligand-dextran conjugates are being explored as a novel therapeutic delivery system.
Purpose of the Study:
- To evaluate the therapeutic potential of ligand-dextran conjugates for targeting EGF receptor-amplified cancers.
- To assess the feasibility of using these conjugates in cancer treatment strategies.
Main Methods:
- EGF or TGF-alpha were conjugated to dextran and evaluated in EGF-receptor amplified glioma cells.
- Conjugates were labeled with radioactive nuclides for detection and some contained boron for Boron Neutron Capture Therapy (BNCT).
- Binding, internalization, retention, and degradation were analyzed, with comparative binding tests against various cancer cell lines.
Main Results:
- Dextran conjugation did not impede receptor-specific binding of the ligands.
- Intracellular retention of radioactive nuclides was significantly improved, lasting 20-24 hours.
- Therapeutic efficacy was enhanced when radioactive iodine-131 was attached to EGF-dextran compared to native EGF.
Conclusions:
- Improved cellular retention of ligand-dextran conjugates provides extended exposure time for radionuclide therapy.
- This enhanced retention offers flexibility in treatment timing and holds potential for Boron Neutron Capture Therapy (BNCT).
- Ligand-dextran mediated BNCT may enable inactivation of locally spread cancer cells that could otherwise escape treatment.