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.
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