What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Bailly, Clément; Gouard, Sébastien; Guérard, François; Chalopin, Benjamin; Carlier, Thomas; Faivre-Chauvet, Alain; Saëc, Patricia Remaud-Le; Bourgeois, Mickaël; Chouin, Nicolas; Rbah-Vidal, Latifa; Tripier, Raphaël; Haddad, Férid; Kraeber-Bodéré, Françoise; Bodet-Milin, Caroline; Chérel, Michel

doi:10.3390/ijms20102564

Cited by 27 publications

(32 citation statements)

References 43 publications

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“…The used antiCD138 mAb was the 9E7.4 mAb, whose characterisation was ensured within our team as previously described [109]. Coupling with TE1PA chelator and radiolabelling with 64Copper was carried out following our standard procedure and as previously reported in recent works [95,113].…”

Section: Discussionmentioning

confidence: 99%

“…Mice bearing subcutaneous MM tumours were imaged using 64Copper-labelled anti-CD38 mAbs with and without a dose of unlabelled mAbs (Figure 1). teams have begun to take an interest in this issue in preclinical studies, including ours [84,85,88,95], and a small first-in-human study was very recently published [88]. Anti-CD38 immunoPET has a high potential in selecting patients and optimal conditions for daratumumab-based treatment.…”

Section: Now What?mentioning

confidence: 99%

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

Bailly

Chalopin

Gouard

et al. 2020

Cancers

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Despite 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.

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Section: Discussionmentioning

confidence: 99%

Section: Now What?mentioning

confidence: 99%

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

Bailly

Chalopin

Gouard

et al. 2020

Cancers

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“…Its specificity has been studied by ELSA assay, cytometry [22] and by immunohistochemistry on skin tissue, spleen tissue, liver tissue and lung tissue. This antibody has also been used with PET imaging to detect MM subcutaneous and intramedular lesions [23,24].…”

Section: Anti-cd138 Antibody 211 At Radiolabeling Immunoreactivity mentioning

confidence: 99%

“…The experimental model was obtained 10 days after intravenous injection of 10 6 5T33 MM cells in C57BL/KaLwRij mice. At this time point, secreted immunoglobulins were undetectable and intramedullary lesions were not yet detectable with PET imaging [21,24]. Then 370, 555, 740 or 1110 kBq of 211 At-9E7.4 mAb was injected intravenously into 16, 10, 17 and 6 mice, respectively.…”

Section: At-anti-mcd138 Tat In a Disseminated Murine MMmentioning

confidence: 99%

Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

Gouard

Maurel

Marionneau-Lambot

et al. 2020

Cancers

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Despite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to destroy the residual cells that cause relapses. A preclinical syngeneic mouse model, consisting of IV injection of 1 million of 5T33 cells in a KaLwRij C57/BL6 mouse, was treated 10 days later with an anti-mCD138 antibody, called 9E7.4, radiolabeled with astatine-211. Four activities of the 211At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (n = 16), 555 kBq (n = 10), 740 kBq (n = 17) and 1100 kBq (n = 6). An isotype control was also tested at 555 kBq (n = 10). Biodistribution, survival rate, hematological parameters, enzymatic hepatic toxicity, histological examination and organ dosimetry were considered. The survival median of untreated mice was 45 days after engraftment. While the activity of 1100 kBq was highly toxic, the activity of 740 kBq offered the best efficacy with 65% of overall survival 150 days after the treatment with no evident sign of toxicity. This work demonstrates the pertinence of treating minimal residual disease of multiple myeloma with an anti-CD138 antibody coupled to astatine-211.

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“…24,25 For copper complexation, the cyclam backbone was selected as the most appropriate since the cavity is better suited for this cation with highly stable and inert complexes being formed; 28,29 it also appeared to be the most tunable platform considering all the recent successful studies in 64 Cu-PET imaging using cyclam-based chelators. 30,31,32,33,34,35 The approach to Glu-CAB-1 Mal was to use the cyclam platform functionalized with two acetate arms, namely TE2A. Although other cyclam derivatives have proved to be more suitable for the application, TE2A presented the advantage of being a decent copper(II) chelator, 36 while offering two remaining secondary amines that could be functionalized ( Figure 2) for passive and active targeting.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

Bihan¹,

Driver²,

Ebenhan³

et al. 2020

Preprint

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In the aim to design small molecules capable of binding in vivo to albumin to form bioconjugates, a second generation GluCAB derivative(Glucose-Chelator-Albumin Bioconjugate) has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue. This series of radioligands - also capable of complexing therapeutic isotopes and therefore classified as theranostic agents - are working on the principle of tumor targeting through the Enhanced Permeability and Retention (EPR) effect as well as glucose metabolism.

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What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Cited by 27 publications

References 43 publications

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

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

Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

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