Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma

Bailly, Clément; Gouard, Sébastien; Lacombe, M.; Saëc, Patricia Remaud-Le; Chalopin, Benjamin; Bourgeois, Mickaël; Chouin, Nicolas; Tripier, Raphaël; Halime, Zakaria; Haddad, Férid; Faivre-Chauvet, Alain; Kraeber‐Bodéré, Françoise; Chérel, Michel; Bodet‐Milin, Caroline

doi:10.18632/oncotarget.23886

Cited by 28 publications

(40 citation statements)

References 38 publications

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“…However, preclinical therapies were conducted on a xenograft model which is not suitable for assessing toxicities related to physiological uptake. Therefore, building on our previous promising results obtained with bismuth-213 or during the imaging of MM with copper-64, we have once more favored CD138 as a target antigen [21][22][23]49]. CD138 or syndecan-1 has long been considered as the most reliable marker of MM and is still widely used for the diagnosis of MM.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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%

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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“…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%

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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“…Labeled antibodies may be used to detect cells in vivo by SPECT, PET, or NIR fluorescence. They have mainly been used for tumor diagnosis, staging or tumor response monitoring (54). It has been reported that labeled antibodies allow the tracking of T cells in vivo (55).…”

Section: Indirect Methods: Labeled Antibodies and Tracersmentioning

confidence: 99%

Cell Tracking in Cancer Immunotherapy

et al. 2020

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The impressive development of cancer immunotherapy in the last few years originates from a more precise understanding of control mechanisms in the immune system leading to the discovery of new targets and new therapeutic tools. Since different stages of disease progression elicit different local and systemic inflammatory responses, the ability to longitudinally interrogate the migration and expansion of immune cells throughout the whole body will greatly facilitate disease characterization and guide selection of appropriate treatment regiments. While using radiolabeled white blood cells to detect inflammatory lesions has been a classical nuclear medicine technique for years, new non-invasive methods for monitoring the distribution and migration of biologically active cells in living organisms have emerged. They are designed to improve detection sensitivity and allow for a better preservation of cell activity and integrity. These methods include the monitoring of therapeutic cells but also of all cells related to a specific disease or therapeutic approach. Labeling of therapeutic cells for imaging may be performed in vitro, with some limitations on sensitivity and duration of observation. Alternatively, in vivo cell tracking may be performed by genetically engineering cells or mice so that may be revealed through imaging. In addition, SPECT or PET imaging based on monoclonal antibodies has been used to detect tumors in the human body for years. They may be used to detect and quantify the presence of specific cells within cancer lesions. These methods have been the object of several recent reviews that have concentrated on technical aspects, stressing the differences between direct and indirect labeling. They are briefly described here by distinguishing ex vivo (labeling cells with paramagnetic, radioactive, or fluorescent tracers) and in vivo (in vivo capture of injected radioactive, fluorescent or luminescent tracers, or by using labeled antibodies, ligands, or pre-targeted clickable substrates) imaging methods. This review focuses on cell tracking in specific therapeutic applications, namely cell therapy, and particularly CAR (Chimeric Antigen Receptor) T-cell therapy, which is a fast-growing research field with various therapeutic indications. The potential impact of imaging on the progress of these new therapeutic modalities is discussed.

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Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma

Cited by 28 publications

References 38 publications

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

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

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

Cell Tracking in Cancer Immunotherapy

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