Monoclonal antibody uptake in B-cell lymphomas: Experimental studies in nude mouse xenografts |
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Authors: | Jörg Schmid Peter Möller Gerd Moldenhauer Bernd Dörken Heiner Bihl Siegfried Matzku |
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Affiliation: | (1) Institut für Radiologie und Pathophysiologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-6900 Heidelberg, Federal Republic of Germany;(2) Institut für Pathology, University of Heidelberg, D-6900 Heidelberg, Federal Republic of Germany;(3) Institut für Immonologie und Genetik, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-6900 Heidelberg, Federal Republic of Germany;(4) Innere Klinik und Poliklinik, University of Heidelberg, Voss-Strasse 2, D-6900 Heidelberg, Federal Republic of Germany;(5) Abteilung für Nuklearmedizin, Radiologisches Zentrum, University of Heidelberg, Im Neuenheimer Feld 400, D-6900 Heidelberg, Federal Republic of Germany;(6) c/o E. Merck, Pharma Forschung IMC, Frankfurter Strasse 250, D-6100 Darmstadt, FRG |
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Abstract: | Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values. |
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Keywords: | Monoclonal antibodies Xenografts B-lymphoma Accessibility Interstitial transport |
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