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Differential penetration of targeting agents into multicellular spheroids derived from human neuroblastoma
R J Mairs1, W J Angerson, J W Babich
1Department of Radiation Oncology, University of Glasgow.
Abstract:
We have used a multicellular tumour spheroid model for determination of the penetration of various targeting agents of potential use in the treatment of neuroblastoma. Both the radiopharmaceutical meta-iodobenzylguanidine (mIBG) and the beta subunit of nerve growth factor (beta-NGF) distributed uniformly throughout spheroids, though the latter was poorly concentrated relative to mIBG. In contrast, the anti-neuroectodermal monoclonal antibody. UJ13A bound only to peripheral cell layers with little accumulation in the spheroid interior. Differential penetration of targeting agents may influence the choice of conjugated radionuclide which is likely to achieve maximum therapeutic benefit.
Insights
We studied how neuroblastoma treatments penetrate tumors using a spheroid model. Uniform penetration was seen with meta-iodobenzylguanidine (mIBG) and beta-nerve growth factor (beta-NGF), unlike antibody UJ13A which only reached the tumor surface.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Molecular Imaging
Background:
- Neuroblastoma is a pediatric cancer.
- Targeting agents are crucial for effective neuroblastoma treatment.
- Understanding agent penetration in tumors is key for therapeutic success.
Purpose of the Study:
- To evaluate the penetration of targeting agents in a multicellular tumor spheroid model for neuroblastoma.
- To compare the distribution of radiopharmaceutical meta-iodobenzylguanidine (mIBG), beta subunit of nerve growth factor (beta-NGF), and monoclonal antibody UJ13A.
Main Methods:
- Utilized a multicellular tumor spheroid model.
- Assessed the penetration and distribution of mIBG, beta-NGF, and UJ13A within spheroids.
Main Results:
- mIBG and beta-NGF showed uniform distribution throughout the spheroids.
- beta-NGF exhibited lower concentration compared to mIBG.
- UJ13A bound to peripheral cell layers, with minimal penetration into the spheroid interior.
Conclusions:
- Differential penetration of targeting agents impacts therapeutic efficacy in neuroblastoma.
- The choice of conjugated radionuclide should consider the penetration characteristics of the targeting agent.
- These findings inform the selection of agents for optimal neuroblastoma treatment strategies.