Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma

2.50
Hdl Handle:
http://hdl.handle.net/10541/71920
Title:
Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma
Authors:
Du, Yong; Honeychurch, Jamie; Glennie, Martin J; Johnson, Peter W; Illidge, Timothy M ( 0000-0003-3191-7324 )
Abstract:
Radioimmunotherapy is a highly effective treatment for some hematologic malignancies; however, the underlying mechanisms of tumor clearance remain poorly understood. We have previously shown that both targeted radiation using (131)I-labeled anti-MHC class II (MHCII) monoclonal antibody (mAb) plus mAb signaling with unlabeled anti-idiotype are required for the long-term clearance of tumor in syngeneic murine lymphoma models. In this study, we have investigated how the microdistribution of the targeted radiation component of this combination affects the long-term clearance of lymphoma. (131)I-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry ( approximately 1.0 Gy per MBq when (131)I was labeled to 500 mug mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, (131)I-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of (131)I-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the (131)I-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of (131)I-anti-CD45 was increased, a radiation dose response was shown in the presence of anti-idiotype and long-term survival was seen. We believe that these new insights should influence the selection of new antigen targets and the design of dosimetric methods in radioimmunotherapy of lymphoma.
Affiliation:
Cancer Sciences Division, School of Medicine, University of Southampton, Southampton, United Kingdom.
Citation:
Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma. 2007, 67 (3):1335-43 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Feb-2007
URI:
http://hdl.handle.net/10541/71920
DOI:
10.1158/0008-5472.CAN-06-2495
PubMed ID:
17283171
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDu, Yong-
dc.contributor.authorHoneychurch, Jamie-
dc.contributor.authorGlennie, Martin J-
dc.contributor.authorJohnson, Peter W-
dc.contributor.authorIllidge, Timothy M-
dc.date.accessioned2009-06-30T11:17:59Z-
dc.date.available2009-06-30T11:17:59Z-
dc.date.issued2007-02-01-
dc.identifier.citationMicroscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma. 2007, 67 (3):1335-43 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid17283171-
dc.identifier.doi10.1158/0008-5472.CAN-06-2495-
dc.identifier.urihttp://hdl.handle.net/10541/71920-
dc.description.abstractRadioimmunotherapy is a highly effective treatment for some hematologic malignancies; however, the underlying mechanisms of tumor clearance remain poorly understood. We have previously shown that both targeted radiation using (131)I-labeled anti-MHC class II (MHCII) monoclonal antibody (mAb) plus mAb signaling with unlabeled anti-idiotype are required for the long-term clearance of tumor in syngeneic murine lymphoma models. In this study, we have investigated how the microdistribution of the targeted radiation component of this combination affects the long-term clearance of lymphoma. (131)I-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry ( approximately 1.0 Gy per MBq when (131)I was labeled to 500 mug mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, (131)I-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of (131)I-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the (131)I-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of (131)I-anti-CD45 was increased, a radiation dose response was shown in the presence of anti-idiotype and long-term survival was seen. We believe that these new insights should influence the selection of new antigen targets and the design of dosimetric methods in radioimmunotherapy of lymphoma.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntibody-Dependent Cell Cytotoxicity-
dc.subject.meshAntigens, CD45-
dc.subject.meshHistocompatibility Antigens Class II-
dc.subject.meshImmunoconjugates-
dc.subject.meshIodine Radioisotopes-
dc.subject.meshLymphoma, B-Cell-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshRadioimmunotherapy-
dc.subject.meshRadiometry-
dc.titleMicroscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphomaen
dc.typeArticleen
dc.contributor.departmentCancer Sciences Division, School of Medicine, University of Southampton, Southampton, United Kingdom.en
dc.identifier.journalCancer Researchen

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