Values are expressed in percentage of the injected radioactive dose per gram of tissue (%ID/g) and presented as mean +/- SD. == 2.2. MM. Keywords:multiple myeloma, immuno-PET, copper-64, zirconium-89, murine CD138 == 1. Introduction == Over the last 30 years, major advances have been made with regard to the management of multiple myeloma (MM) [1,2]. These improvements have occurred along with our evolving understanding of this malignancy [3]. Multi-clonal heterogeneity of MM Omeprazole still remains one of the main challenges in developing effective therapeutic strategies [4]. Immunologic approaches represent an attractive solution to address this issue for treatment [5], however also for imaging [6] in the context of theranostic approaches. Indeed, the combination of positron emission tomography (PET) with monoclonal antibodies (mAbs) enables the realisation of a specific imaging called immuno-PET [7]. Among the interesting targets, CD138 or syndecan-1 is a cell surface proteoglycan that plays a critical role in the interaction between MM cells and their microenvironment [8,9]. This antigen is currently used as a standard marker for the identification and purification of MM cells in daily practice. Anti-CD138 immuno-PET thus has the potential to improve MM imaging, especially regarding lesions with low metabolic activity [10,11]. Moreover, it could also be considered as a companion agent for currently developed therapies targeting CD138 [12,13]. In the past several years, our group has also proven that radioimmunotherapy (RIT) combining anti-CD138 mAb and alpha-emitters radionuclides is effective in an immuno-competent preclinical MM model and is feasible in humans [14,15]. For immuno-PET, the choice of the radionuclides remains a fundamental question [7]. Combining appropriate half-lives for mAbs biodistribution and favorable emission properties for imaging, Copper-64 (64Cu) and Zirconium-89 (89Zr) have monopolized much of the researchers attention during the last decade with an advantage for the second one in terms of number of studies [16,17]. However, reported release of89Zr from the imaging probe may represent a drawback for bone lesions imaging [18] and therefore for MM assessment. In this work, we report the preclinical evaluation of a novel PET imaging agent based on the89Zr-labeled anti-mouse syndecan-1 mAb (9E7.4, IgG2a isotype) [19] in a subcutaneous model and a bone marrow disseminated MM model using desferrioxamine B (DFO) as chelator. This is compared to18F-FDG-PET and bioluminescence imaging as gold standards and to89Zr-oxalate imaging as a control of potential89Zr release by the chelator agent. Furthermore, given COL4A1 our previous experience using64Cu [11] and to establish the optimal radiolabeled 9E7.4 mAb for immuno-PET, biodistribution and PET imaging in vivo of89Zr- and64Cu-mAb conjugates have been compared with emphasis on bone uptake. == 2. Results == To evaluate and select the optimal radiolabeled 9E7.4 mAb for immuno-PET of MM lesions in bones, we have generated two radio-immunoconjugates PET tracers (89Zr-DFO-9E7.4 and64Cu-TE2A-9E7.4). Biodistribution and imaging studies were performed. This report focuses on PET Omeprazole imaging with89Zr-DFO-9E7.4 and follows a recent published work on64Cu-TE2A-9E7.4 [11]. However, comparison between both in a disseminated model is presented. == 2.1. Ex Vivo Biodistribution Experiments == Ex vivo biodistribution at 24 h and 72 h post-injection (PI) results are presented inFigure 1andTable 1. On the study conducted 24 h after administration of89Zr-DFO-9E7.4 (Figure 1A,B) in a subcutaneous model of MM, the tracer displayed correct accumulation in the tumors which decreased at 72 h PI.89Zr-DFO-9E7.4 showed significant blood clearance from 24 h PI to 72 h PI, resulting in increased tumor-to-blood ratios. The radio-immunoconjugate also showed relative high uptakes of89Zr-DFO-9E7.4 in several normal organs such as liver, spleen and guts. Low muscle uptake was found at both 24 h and 72 h PI. All other organs displayed Omeprazole activity concentrations of 5 %ID/g or less at 24 h with decreasing activity Omeprazole at 72 h PI. Only flat bones.