Radioimmunotherapy has proven clinically effective in patients with
non-Hodgkin's lymphoma.
Radioimmunotherapy trials have so far been performed with beta-emitting
isotopes. In contrast to beta-emitters, the shorter range and high linear energy transfer (LET) of alpha particles allow for more efficient and selective killing of individually targeted
tumor cells. However, there are several obstacles to the use of alpha-particle
immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The alpha-emitting
radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab is a new potential anti-
lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel
radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the alpha-particle-emitting nuclide (227)Th alone, the chelated form, (227)Th-p-nitrobenzyl-DOTA and the
radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of (227)Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of
radioimmunoconjugate only, very modest amounts of the (227)Th had detached from
DOTA-p-benzyl-
rituximab, indicating a relevant stability in vivo. The half-life of (227)Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of
lymphoma cells with (227)Th-DOTA-p-benzyl-rituximab resulted in a significant
antigen-dependent inhibition of cell growth. The data presented here warrant further studies of (227)Th-DOTA-p-benzyl-rituximab.