This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Du, Y. Articles by Illidge, T. Search for Related Content PubMed PubMed Citation Articles by Du, Y. Articles by Illidge, T.

Microscopic Intratumoral Dosimetry of Radiolabeled Antibodies Is a Critical Determinant of Successful Radioimmunotherapy in B-Cell Lymphoma

¹ Cancer Sciences Division, School of Medicine, University of Southampton, Southampton, United Kingdom; ² Cancer Studies Division, Cancer Research UK Paterson Institute, School of Medicine, University of Manchester, Manchester, United Kingdom; and ³ Institute of Nuclear Medicine, University College London Hospital, London, United Kingdom

Requests for reprints: Tim Illidge, Cancer Studies Division, School of Medicine, University of Manchester, Manchester M20 4BX, United Kingdom. Phone: 44-161-446-8095; Fax: 44-161-446-8111; E-mail: tmi{at}manchester.ac.uk.

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 ¹³¹I-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. ¹³¹I-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry (1.0 Gy per MBq when ¹³¹I was labeled to 500 µg mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, ¹³¹I-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of ¹³¹I-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the ¹³¹I-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of ¹³¹I-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. [Cancer Res 2007;67(3):1335–43]