213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Radioimmunotherapy (RIT) with beta-emetting emitting radionuclides is a promising treatment in lymphoma. Though However, the efficiency of beta-emitting radionuclides to kill isolated tumor cells is limited by the relatively long range of beta radiation in human tissue, resulting in deposition of most of the beta particle energy far from the targeted cell. For disease such as leukemia and for residual disease, the use of alpha emitters which deliver large amounts of energy (several MeV) in an area of less than 100 µm has been developed. Alpha emitting radionuclides such as 213Bi or 211At have short half-lives and therefore require a rapid targeting of the tumor. In this context, alpha RIT appears as a particularly attractive therapy in multiple myeloma (MM). Indeed, in MM since the marrow shows diffuse or focal radiosensitive plasma cells involvement, the use of a specific vector coupled with high energy particles such as alpha shall enable localized destruction of myeloma cells with limited damages to surrounding healthy tissues. Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on tumor cells in MM. Therefore this surface antigen is an attractive candidate for targeted therapy. The aim of the study was to assess toxicity and efficacy of RIT using 213Bi-anti-mCD138 in a murine MM model. The model was obtained using the 5T33 line that spontaneously occurred in C57BL/KaLwRij mice and has been propagated in vivo by intravenous transfer into young syngeneic recipients. Mice were treated using 213Bi-anti-mCD138 at 4 injected activities (1.85, 3.7, 7.4 and 11.1 MBq). Groups treated with 3.7 and 7.4 MBq exhibited a median survival above 300 days and 227 days respectively compared to 45.5 days in control group. The highest activity (11.1 MBq) was rapidly toxic while the lowest activity (1.85 MBq) gave results similar to the control. With activities of 3.7 and 7.4 MBq, surviving mice exhibit a transient hematological toxicity and we observed at 7.4 MBq only, a temporary sign of low myelotoxicity. This study demonstrated excellent therapeutic efficacy of 213Bi-anti-mCD138 RIT in MM.

CHEREL M.;  GOUARD S.;  GASCHET J;  SAÏ-MAUREL C;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  BOURGEOIS N.;  GESTIN J.F.;  KRAEBER BODÉRÉ F;  BARBET J;  MOREAU P;  DAVODEAU F.; 

2013-10-02

SOC NUCLEAR MEDICINE INC

JRC65535

0161-5505,   

http://jnm.snmjournals.org/content/54/9/1597,    https://publications.jrc.ec.europa.eu/repository/handle/JRC65535,   

10.2967/jnumed.112.111997,