Abstract
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, 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 time. 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 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.
Keywords: Antibodies, cytostatic drugs, epidermal growth factor, metastases, penetration, review, spheroids, tumor cells
Current Cancer Therapy Reviews
Title: Penetration of Tumor Therapy Interesting Substances in Non-Vascularized Metastases: Review of Studies in Multicellular Spheroids
Volume: 2 Issue: 4
Author(s): Jorgen Carlsson and Lars Gedda
Affiliation:
Keywords: Antibodies, cytostatic drugs, epidermal growth factor, metastases, penetration, review, spheroids, tumor cells
Abstract: 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, 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 time. 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 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.
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Carlsson Jorgen and Gedda Lars, Penetration of Tumor Therapy Interesting Substances in Non-Vascularized Metastases: Review of Studies in Multicellular Spheroids, Current Cancer Therapy Reviews 2006; 2 (4) . https://dx.doi.org/10.2174/157339406778699213
DOI https://dx.doi.org/10.2174/157339406778699213 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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