Unprecedented incorporation of α-emitter radioisotope 213Bi into porphyrin chelates with reference to a daughter isotope mediated assistance mechanism.

International audienceFor the first time, α-emitter radioisotope (213)Bi has been incorporated into porphyrin chelates, with rates matching with the short period of the radionuclide. An in situ transmetalation mechanism involving the daughter isotope (209)Pb is expected to boost the (213)Bi radiolabeling process

Unprecedented Incorporation of alpha-Emitter Radioisotope 213Bi into Porphyrin Chelates with Reference to a Daughter Isotope Mediated Assistance Mechanism

For the first time, alphaemitter radioisotope 213Bi has been 10 incorporated into porphyrin chelates, with rates matching with the short period of the radionuclide. An in-situ transmetalation mechanism involving the daughter isotope 209Pb is expected to boost the 213Bi radiolabeling process.JRC.E.5-Nuclear chemistr

Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

International audienceTargeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR). Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy

ImmunoPET in Multiple Myeloma—What? So What? Now What?

International audienceDespite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET

PET Imaging of Multiple Myeloma : Comparison of 89Zr- and 64Cu-labeled anti-CD138 Conjugates to 64CuCl2 and 18F-FDG in a Preclinical Syngeneic Model

Abstracts of Annual Congress of the European Association of Nuclear Medicine October 13 – 17, 2018 Düsseldorf, GermanyInternational audiencePurpose: Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated 2 conjugates of an anti-CD138 murine antibody (9E7.4) and compared them to metabolic tracers (64CuCl2and 18F-FDG) for PET imaging in a MM syngeneic mouse model. Subjects and Methods: 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for copper-64 (64Cu) and zirconium- 89 (89Zr) labeling. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies and 64CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. Results: In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and89Zr-DFO-9E7.4displayed comparable good tumor uptake of subcutaneous tumors. On the opposite, only low-level concentrations of 64CuCl2 were accumulated in MM lesions. PET/CT imaging of the disseminated model with 64Cu TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed high uptake of the probes at the site of intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET and correlating with the bioluminescence imaging of the tumor. Histopathologic analysis of the immuno-PET-positive lesions also confirmed the presence of plasma cell infiltrates within the bone marrow. Comparison of both 9E7.4 conjugates revealed higher non specific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4 (3.1±1.15 vs 1.48±0.29 respectively at 24h PI; p=0.0061; non-parametric test) while the opposite was observed for tumor-to-blood ratio (1.42±0.24 vs 4.08±1.09 respectively at 24h PI; p=0.0391; non-parametric test). Such observations were consistent with the known in vivo gradual transchelation of 89Zr over time which could reduce the efficacy of a 89Zr-labeled immuno-PET probe as an effective tool for bone lesions imaging. Conclusion: 64Cu- and 89Zr-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18F-FDG-PET and 64CuCl2 in this preclinical model. 64Cu- anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific and promising new imaging radiopharmaceutical agent in MM