Abstract 714: Non-invasive monitoring of the antitumor activity of SAR650984 anti-CD38 antibody against disseminated human Daudi lymphoma using 18F-FDG micro Positron Emission Tomography
Authors: Besret Laurent D.D. , D'Heilly Sébastien , Selingue Alain , Lejeune Pascale , Vrignaud Patricia , Bissery Marie-Christine , Carrez Chantal 
Published: February 2011

Abstract
Positron Emission Tomography (PET) using [18F]-fluoro-deoxyglucose (FDG) is rapidly gaining acceptance in the clinics for the follow-up of anticancer therapies. Similarly in preclinical studies FDG-μPET could enable non-invasive monitoring of orthotopic or disseminated tumor models. The aim of this study was to assess the suitability of FDG-μPET imaging for the evaluation of the humanized anti-CD38 antibody SAR650984, currently in development, in mice bearing disseminated human lymphoma Daudi. Methods: Female SCID mice were implanted via the tail vein with human lymphoma Daudi cells. In the treatment groups, SAR650984 was administered by the IV route at 40mg/kg in a “prevention” protocol (e.g. before appearance of quantifiable PET signal) or in an “intervention” protocol (e.g. with quantifiable PET signal at baseline). In the vehicle (n=8) and in the SAR650984 groups (n=6), the treatment was given on a q2w schedule for 3 weeks. Serial FDG-PET imaging was performed regularly from day 11-32, 11-56 and 25-133 for control, prevention and intervention groups, respectively. Antitumor efficacy was determined by evaluating the increase in lifespan (ILS) calculated as the delay for median day of death in the treated group relative to the control. Results: SAR650984 was well tolerated at the highest dose tested of 40 mg/kg/adm x 6 adm with 6% and 12% body weight loss at nadir for prevention and intervention protocols, respectively. In the prevention group, SAR650984 was active with 131% ILS and significant delayed tumor glucose uptake: whereas signal could be detected in the PET experiment on day 25 in 8/8 control animals in kidney and ovary target organs, no significant FDG uptake occurred for mice in the prevention before day 39. The signal being quantifiable from day 39 onwards, the delay in FDG uptake between treated and control group was estimated to be 14 days. In the intervention group in which animals were treated with SAR650984 at an advanced stage of disease according to PET (e.g. with measurable FDG signal in target organ Region Of Interest [ROI]), 2 of 6 animals outlived the control group. FDG-PET imaging of the first mouse showed stable tracer uptake within ROI during treatment with an increase in the ovarian region at the end of treatment correlating with the presence of tumors at necropsy (day 88). The second mouse exhibited complete regression of the signal with no resurgence in concordance with the gross necropsy on day 133 showing no hints of tumor invasion in the target organs. Conclusion: The data demonstrates that SAR650984 therapy affects tumor metabolic activity in the disseminated Daudi lymphoma model. FDG-PET imaging thus appears as a valuable functional readout for longitudinal monitoring of anti-CD38 mAb SAR650984 pharmacological activity in the preclinical setting and may provide a mean to follow SAR650984 efficacy in clinic.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 714.