Preparation of TH²²⁷-Labeled Radioimmunoconjugates, Assessment of Serum Stability and Antigen Binding Ability

Abstract

In this study, the feasibility of constructing radioimmunoconjugates by using the novel therapeutic candidate alpha-emitter, 227 Th, was evaluated. By use of the bifunctional chelator, p-SCN-benzyl-DOTA, 227 Th was conjugated to the two monoclonal antibodies, rituximab and trastuzumab. Their stability in 80% fetal bovine serum at 37°C was measured. The immunoreactive fractions were determined by using CD20and HER/2-positive cells, respectively. The overall labeling yield spanned from 6% to 17%. The radioimmunoconjugates demonstrated a relevant stability in serum and showed appropriate antigen-binding abilities.

Targeted cancer therapy with a novel low-dose rate α-emitting radioimmunoconjugate

“…20 Cell concentrations of up to 10 8 Raji cells/mL were used to compensate for the modest specific activity of the RIC. 13,16 The immunoreactive fractions of conjugates used in the current study were between 56% and 65%.…”

“…13,16,19 The specific activity of the RIC was in the range of 650 to 5300 Bq/g. The quality of the RIC was assessed using lymphoma cells and a modified Lindmo and Bunn method.…”

Targeted use of Alpha Particles: Current Status in Cancer Therapeutics

“…Free thorium deposits predominantly in bone, and the uptake in the bone of 227 Th-p-nitrobenzyl-DOTA has been demonstrated to be seven times lower than that of free thorium [30]. Subsequent efforts have also succeeded in creating a similar radioimmunoconjugate by binding 227 Th to trastuzumab via p-iso-thiocyanato-benzyl-DOTA [29,[47][48][49].…”

Treatment of HER2-Expressing Breast Cancer and Ovarian Cancer Cells With Alpha Particle-Emitting 227Th-Trastuzumab

“…Trastuzumab was labeled with 227 Th, as described previously (10), and using two other slightly different methods as well as with fluorescent dyes. The immunoreactive fraction was calculated as the fraction of cell-bound activity in the unblocked samples minus the unspecific cell-bound activity in the blocked control (see supplementary Table E2).…”