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Herrmann, K., Buck, A.K., Schuster, T., Abbrederis, K., Blümel, C., Santi, I., Rudelius, M., Wester, H.J., Peschel, C., Schwaiger, M., Dechow, T. and Keller, U. (2014) Week One FLT-PET Response Predicts Complete Remission to R-CHOP and Survival in DLBCL. Oncotarget, 5, 4050-4059.

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• TITLE: Preclinical Evaluation of CD40-Directed Immunotherapy in B-Cell Lymphoma Using [18F]Fluorothymidine-PET

  AUTHORS: Nicolas Graf, Zhoulei Li, Ken Herrmann, Michaela Aichler, Jolanta Slawska, Axel Walch, Christian Peschel, Markus Schwaiger, Andreas K. Buck, Tobias Dechow, Ulrich Keller

  KEYWORDS: CD40 Antibody, FLT-PET, Lymphoma, Therapy Monitoring

  JOURNAL NAME: Advances in Molecular Imaging, Vol.5 No.2, April 9, 2015

  ABSTRACT: 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.