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The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen.Its potential as a radioimmunotargeting agent, as well as its safety, has beenshown in previous studies in head and neck cancer patients. However, intact MAbshave long circulation time in the blood and tumor targeting may also be hampereddue to the slow and incomplete diffusion into solid tumors. In comparison, smallermonovalent Fab' and divalent F(ab')2 fragments are expected to exhibit shortercirculating half-lives, better tumor penetration and are thus more likely to yieldbetter imaging results. In this study, novel F(ab')2 and Fab' fragments from cMAbU36 were radiolabeled with 125I and the characteristics of the conjugates in vitrowere examined. The biodistribution of the conjugates were then evaluated in nudemice bearing CD44v6-expressing xenograft tumors. Furthermore, the penetrationdepth and distribution in tumor tissue was assessed by autoradiography in selectedtumor samples. The in vitro experiments showed that the conjugates were stableand had intact affinity to CD44v6. The biodistribution study demonstrated superiortumor-to-blood ratio for the novel cMAb U36 fragment 125I-F(ab')2 compared withboth the intact MAb and the monovalent fragment form. Autoradiography also revealedbetter tumor penetration for 125I-F(ab')2. This study demonstrates that the useof antibody fragments may improve radioimmunotargeting and possibly improve themanagement of head and neck malignancies.

A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio