The goal of this project is to develop the optimum clinical agent for radioimmunoscintigraphy. The optimum nuclide is undoubtedly technetium- 99m. Comparing IgG-SH, F(ab')2-SH and Fab'-SH, it is expected that a F(ab')2-SH fragment will have fast enough clearance from circulation to permit earlier imaging than a comparably radiolabeled IgG-SH while having less renal uptake than a comparably labeled Fab'-SH fragment. Previously, direct labeling of F(ab')2-SH was problematic in that a 50:50 mixture of Tc-99m-F(ab')2 and Tc99m-Fab' would result due to the presence of a small amount of monovalent fragment. We have a novel technique of pre.reducing intact IgG to break non-hinge region disulfide bonds prior to digestion of antibody. The resulting, pure F(ab')2-SH is capable of quantitative incorporation of technetium-99m, in the same manner as IgG-SH and Fab'-SH, are currently labeled, to yield quantitatively Tc-99m-F(ab')2. We will extend the technique to different antibodies targeted against different cancers, and ultimately use humanized F(ab')2-SH fragments. In phase l research, we will to prove the superiority of Tc99m-F(ab'), over Tc-99m- Fab' and Tc-99m-IgG as an early time-point radioimmunoimaging agent; and if successful, produce clinically usable kits at the conclusion of the phase II period.
| Griffiths, G L; Goldenberg, D M; Jones, A L et al. (1994) Preparation of a pure 99mTc-F(ab')2 radioimmunoconjugate by direct labeling methods. Nucl Med Biol 21:649-55 |
