Imaging of the distribution of (90)y-ibritumomab tiuxetan in bone marrow and comparison with pathology.
OBJECTIVE
Radioimmunotherapy with anti-CD20 antibodies (Abs) labeled with beta-emitters is now used in the treatment of non-Hodgkin's lymphoma (NHL). Because (90)Y is a pure beta-emitter, no direct image of its distribution can be obtained in humans. In this paper, we present in this study imaging data of (90)Y-Ab distribution in human-mantle-cell lymphoma within a mouse model. Describing the actual distribution of the radionuclide at the level of particles range may have important impact on patient dosimetry and therapy treatment planning.


METHODS
NOD/SCID mice were grafted with a human NHL cell line that involves the bone marrow. The mice were treated with (90)Y-ibritumomab tiuxetan (Zevalin); Schering AG, Germany) and sacrificed 2 hours after Zevalin administration. Tissue sections were then prepared and viewed under conventional microscopy. The distribution of the radioactivity in mouse femur was determined by using digital autoradiography and subsequently correlated with immunohistochemical results.


RESULTS
Various extent of bone marrow infiltration was investigated and found to be reproducible. Zevalin uptake was heterogeneous within the bone marrow. However, unspecific mouse monoclonal uptake by accessory myeloid cells gave nonspecific background radioactivity. Treating mice with an irrelevant mouse IgG1 monoclonal antibody (mAb) before Zevalin injection controlled this unspecific uptake, and images were strongly correlated with bone marrow infiltration on histologic analysis.


CONCLUSIONS
Our model was reproducible, and allows for the study of various bone marrow involvement with good sensitivity. We demonstrated that imaging of the beta-emitter was possible with good image quality and that (90)Y-Zevalin is distributed heterogeneously within bone marrow. These data suggest that detailed pharmacokinetics may be developed with this model.
Coulot
Jeremy
J
Department of Physics, Institut Gustave-Roussy, Villejuif, France.
Camara-Clayette
Valérie
V
Ricard
Marcel
M
Lavielle
Frédéric
F
Velasco
Valérie
V
Drusch
Françoise
F
Bosq
Jacques
J
Schlumberger
Martin
M
Ribrag
Vincent
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001345:Autoradiography; D001666:Binding Sites, Antibody / Q000276:immunology; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015260:Neprilysin / Q000276:immunology; D016499:Radioimmunotherapy / Q000379:methods; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; C422802:ibritumomab tiuxetan; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D015260:Neprilysin