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Penetration of tumor therapy interesting substances in non-vascularized metastases; Review of studies in cellular spheroids
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. BMS. (BMS)
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. BMS. (BMS)
2006 (English)In: Current Cancer Therapy Reviews, Vol. 27, 293-304 p.Article in journal (Refereed) Published
Abstract [en]

Penetration properties, studied in multicellular spheroids, of totally 23 radiolabeled or boronated substances are summarized. The spheroids were models for small non-vascularized metastases and there is special emphasis on results obtained with a freeze-drying method. The substances were detected using autoradiography or neutron capture radiography. Certain substances, e.g. 5-FU, glucose, BSH and one antibody type, penetrated efficiently while others, e.g. vinblastine, an epidermal growth factor derivative and two other types of antibodies, only penetrated into the outer periphery of the spheroids in spite of long incubation times. The molecular weight of the substances did not relate well with the penetration properties. Instead, those substances that bound extensively had in most cases limited penetration. This was, for example, clearly shown for the drug Ara-C when applied to two different types of spheroids, one type giving low binding and good penetration and one type giving extensive binding and less penetration. The penetration of an antibody and an EGF-derivative improved significantly when their binding sites were blocked. It is concluded that molecular weight is not a dominating determinant for penetration in the studied model, but that binding is. Such knowledge is valuable for the understanding of effects of chemotherapy, targeted radionuclide therapy and immunotherapy and for the development of new agents for such therapies.

Place, publisher, year, edition, pages
2006. Vol. 27, 293-304 p.
Keyword [en]
Antibodies/immunology/therapeutic use, Brachytherapy/*methods, Brain Neoplasms/immunology/metabolism/*radiotherapy, Cell Movement, Glioblastoma/immunology/metabolism/*radiotherapy, Humans, Radioimmunotherapy/*methods, Receptor; Epidermal Growth Factor/immunology/*metabolism, Tissue Distribution
Identifiers
URN: urn:nbn:se:uu:diva-25332OAI: oai:DiVA.org:uu-25332DiVA: diva2:53106
Available from: 2007-02-12 Created: 2007-02-12 Last updated: 2011-01-11

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Carlsson, JörgenGedda, Lars

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