Author(s)

Nicolas Graf^1*, Zhoulei Li², Ken Herrmann^2,3, Michaela Aichler⁴, Jolanta Slawska¹, Axel Walch⁴, Christian Peschel^1,5, Markus Schwaiger^2,5, Andreas K. Buck^2,3, Tobias Dechow¹, Ulrich Keller^1,5

¹III. Medical Department of Hematology and Medical Oncology, Technische Universitat München, Munich, Germany.
²Department of Nuclear Medicine, Technische Universitat München, Munich, Germany.
³Department of Nuclear Medicine, Universitat Sklinikum Würzburg, Würzburg, Germany.
⁴Institute of Pathology—Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
⁵German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Inhibition of the lymphoma surface antigen CD40 by the antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various lymphoma subtypes. In this preclinical in vivo study we examined the suitability of positron emission tomography (PET) using the thymidine analogue 3’-deoxy-3’-[¹⁸F]fluorothymidine (FLT) for early response assessment upon HCD122 treatment in diffuse large B cell lymphoma (DLBCL). Methods: Immunodeficient mice bearing human DLBCL xenografts (SU-DHL-4) received weekly intraperitoneal injections of HCD122. Tumor growth was followed up until Day 14. Molecular imaging with FLT-PET was performed before (Day 0) and after start of therapy (Day 2 and Day 7). On Day 14 lymphoma xenografts were explanted for immunohistochemical analysis to correlate PET findings with CD40 surface expression on tumor tissue. Results: Treatment with HCD122 significantly delayed tumor growth resulting in a tumor growth inhibition of 45% on Day 14. Significant reduction of tumor-to-background ratio (TBR) of FLT-PET was seen in treated animals on Day 7 and preceded change of tumor volume, thus predicting therapy response to HCD122. Immunohistochemical analysis of xenografts revealed significantly higher CD40 expression on treated than on untreated tissue. Moreover, we found a significant correlation between CD40 expression and FLT-PET response for xenograft tumor treated with HCD122. Conclusions: Treatment of DLBCL with the antagonistic CD40 antibody HCD122 can be monitored with FLT-PET as early as seven days after commencement of therapy and seems to increase CD40 expression on tumor tissue.

CD40 Antibody, FLT-PET, Lymphoma, Therapy Monitoring

Graf, N. , Li, Z. , Herrmann, K. , Aichler, M. , Slawska, J. , Walch, A. , Peschel, C. , Schwaiger, M. , Buck, A. , Dechow, T. and Keller, U. (2015) Preclinical Evaluation of CD40-Directed Immunotherapy in B-Cell Lymphoma Using [¹⁸F]Fluorothymidine-PET. Advances in Molecular Imaging, 5, 17-28. doi: 10.4236/ami.2015.52002.