Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy

Gouard, Sébastien; Pallardy, Amandine; Gaschet, Joëlle; Faivre-Chauvet, Alain; Bruchertseifer, Frank; Morgenstern, Alfred; Maurel, Catherine; Matous, Etienne; Kraeber-Bodéré, Françoise; Davodeau, François; Chérel, Michel

doi:10.1016/j.nucmedbio.2014.02.008

Cited by 28 publications

(16 citation statements)

References 29 publications

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“…The present work demonstrated the high targeted-tumor uptake of 64 Cu-TE2A-9E7.4 in MM tumor-bearing mice. Based on our experience with the B-B4 mAb [ 24 , 25 ], our group had developed this rat anti-mouse syndecan mAb (9E7.4, IgG2a κ isotype) that specifically recognizes the extracellular domain of mouse syndecan-1 [ 26 ]. This study showed that 64 Cu-TE2A-9E7.4 binds effectively to CD138 tumors and allows MM imaging in a syngeneic mouse model with high contrast.…”

Section: Discussionmentioning

confidence: 99%

“…The 5T33 murine MM cell line was kindly provided by Dr. Harvey Turner (Nuclear Medicine Service, Fremantle Hospital, Western Australia) with the permission of Dr. Jiri Radl (TNO Institute, Leiden, Netherlands) [ 38 ]. Cells were transfected with luciferase cDNA as previously described [ 25 ]. 5T33-Luc(+) were cultured in RPMI1640 medium (Gibco, Saint Aubin, France) containing 2 mM L-glutamine and 10% heat-inactivated fetal calf serum (PAA Laboratories / GE Healthcare Europe GmbH) at 37°C, 5% CO 2 , 95% humidity.…”

Section: Methodsmentioning

confidence: 99%

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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

et al. 2018

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PurposeAlthough 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 a 64Cu-labeled anti-CD138 murine antibody (64Cu-TE2A-9E7.4) and a metabolic tracer (64CuCl2) for PET imaging in a MM syngeneic mouse model.Experimental Design and Results64Cu-TE2A-9E7.4 antibody 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. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET. In control experiments, only low-level, non-specific uptake of 64Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of 64CuCl2 were accumulated in MM lesions. Histopathologic analysis of the immuno-PET–positive lesions revealed the presence of plasma cell infiltrates within the bone marrow.Conclusions64Cu-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. These data support 64Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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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%

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 Protracted suppression of osteoblast differentiation could result in MM disease. 24 Protracted suppression of osteoblast differentiation could result in MM disease.…”

Section: Discussionmentioning

confidence: 99%

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Wei

Chen

et al. 2018

J of Cellular Biochemistry

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Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray‐based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co‐operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway–related genes, EMX2 and osteoblast differentiation‐related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co‐operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co‐operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.

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Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy

Cited by 28 publications

References 29 publications

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

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

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

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

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