Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma
Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma
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 I-131-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. I-131-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry (similar to 1.0 Gy per MBq when I-131 was labeled to 500 mu g mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, I-131-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of I-131-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the I-131-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of I-131-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 radioinimnnotherapy of lymphoma.
leukemia, cancer, biodistribution, non-hodgkins-lymphoma, survival, tumor-cells, mechanism, model, lymphoma, radiation, clinical radioimmunotherapy, cell, cells, quantitative autoradiography, b cell, i-131, sections, antigen, mouse, time, monoclonal-antibodies, models, monoclonal antibody
1335-1343
Du, Yong
5ae897d7-a3db-45d7-896a-187afa95ac43
Honeychurch, Jamie
4ecce821-9d37-4c35-bcb3-871ff832a3d2
Glennie, Martin
9f6f0eff-4560-48c2-80cd-0ec116110ded
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Illidge, Tim
50e3482f-405f-4534-8062-180bba1c1619
February 2007
Du, Yong
5ae897d7-a3db-45d7-896a-187afa95ac43
Honeychurch, Jamie
4ecce821-9d37-4c35-bcb3-871ff832a3d2
Glennie, Martin
9f6f0eff-4560-48c2-80cd-0ec116110ded
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Illidge, Tim
50e3482f-405f-4534-8062-180bba1c1619
Du, Yong, Honeychurch, Jamie, Glennie, Martin, Johnson, Peter and Illidge, Tim
(2007)
Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma.
Cancer Research, 67 (3), .
(doi:10.1158/0008-5472.CAN-06-2495).
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 I-131-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. I-131-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry (similar to 1.0 Gy per MBq when I-131 was labeled to 500 mu g mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, I-131-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of I-131-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the I-131-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of I-131-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 radioinimnnotherapy of lymphoma.
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Published date: February 2007
Keywords:
leukemia, cancer, biodistribution, non-hodgkins-lymphoma, survival, tumor-cells, mechanism, model, lymphoma, radiation, clinical radioimmunotherapy, cell, cells, quantitative autoradiography, b cell, i-131, sections, antigen, mouse, time, monoclonal-antibodies, models, monoclonal antibody
Identifiers
Local EPrints ID: 62725
URI: http://eprints.soton.ac.uk/id/eprint/62725
ISSN: 0008-5472
PURE UUID: 8716fc3c-a0fa-4817-8cbe-ca88e1c6ac5e
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Date deposited: 16 Apr 2009
Last modified: 16 Mar 2024 02:59
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Author:
Yong Du
Author:
Jamie Honeychurch
Author:
Tim Illidge
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