Radionuclides linked to a CD74 antibody as therapeutic agents for B-cell lymphoma: comparison of Auger electron emitters with beta-particle emitters.
We demonstrated previously that human B-cell lymphomas were effectively and specifically killed in vitro by an antibody to CD74 (LL1) linked to (111)In or other Auger electron emitters. This study was intended to more accurately compare the potency and specificity of 3Auger electron emitters, (111)In, 67Ga, and 125I, and to evaluate beta-particle emitters, 131I and 90Y. The unique property of LL1 is its high level of intracellular uptake.


METHODS
Raji B-lymphoma cells were incubated with serial dilutions of the radiolabeled Abs for 2 d and then monitored for cell growth by 2 assays: a cell counting assay and a clonogenic assay. The uptake of radioactivity per cell was monitored at various time points, and the radiation dose was calculated using published S values for radioactivity located in the cytoplasm. Both specific and nonspecific toxicity were evaluated.


RESULTS
The beta-particle emitters had considerably higher levels of nonspecific toxicity than the Auger electron emitters, but both 131I and 90Y, and particularly 131I, still had high levels of specificity. Both of these results were consistent with dosimetry calculations. Relative to the delivered disintegrations per cell, 131I and 67Ga were the most potent of the radionuclides tested, with 125I and (111)In being significantly weaker and 90Y being intermediate. The high potency of 67Ga, together with its low nonspecific toxicity, caused this radionuclide to have the highest specificity index.


CONCLUSIONS
When delivered by Ab LL1, both Auger electron and beta-particle emitters can produce specific and effective toxicity. The choice of the optimal radionuclide for therapy may depend on the ease and efficiency of labeling, the specific activity obtained, the nature of the tumor being targeted, and other factors, but the high specificity indices of the Auger electron emitters may be an advantage.
Govindan
S V
SV
Immunomedics, Inc., Morris Plains, New Jersey, USA.
Goldenberg
D M
DM
Elsamra
S E
SE
Griffiths
G L
GL
Ong
G L
GL
Brechbiel
M W
MW
Burton
J
J
Sgouros
G
G
Mattes
M J
MJ
D000906:Antibodies; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001610:Beta Particles; D002470:Cell Survival; D004583:Electrons; D005710:Gallium Radioisotopes / Q000627:therapeutic use; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007205:Indium Radioisotopes / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D005710:Gallium Radioisotopes; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; C045084:invariant chain