A novel CD44v6 targeting antibody fragment with improved tumor-to-blood             ratio.
The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen.             Its potential as a radioimmunotargeting agent, as well as its safety, has been             shown in previous studies in head and neck cancer patients. However, intact MAbs             have long circulation time in the blood and tumor targeting may also be hampered             due to the slow and incomplete diffusion into solid tumors. In comparison, smaller             monovalent Fab' and divalent F(ab')2 fragments are expected to exhibit shorter             circulating half-lives, better tumor penetration and are thus more likely to yield             better imaging results. In this study, novel F(ab')2 and Fab' fragments from cMAb             U36 were radiolabeled with 125I and the characteristics of the conjugates in vitro             were examined. The biodistribution of the conjugates were then evaluated in nude             mice bearing CD44v6-expressing xenograft tumors. Furthermore, the penetration             depth and distribution in tumor tissue was assessed by autoradiography in selected             tumor samples. The in vitro experiments showed that the conjugates were stable             and had intact affinity to CD44v6. The biodistribution study demonstrated superior             tumor-to-blood ratio for the novel cMAb U36 fragment 125I-F(ab')2 compared with             both the intact MAb and the monovalent fragment form. Autoradiography also revealed             better tumor penetration for 125I-F(ab')2. This study demonstrates that the use             of antibody fragments may improve radioimmunotargeting and possibly improve the             management of head and neck malignancies.
Department of Surgical Sciences, Unit of Otolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden. karl.sandstrom@surgsci.uu.se
K
K
Sandström
A K
AK
Haylock
D
D
Spiegelberg
F
F
Qvarnström
K
K
Wester
M
M
Nestor
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006207:Half-Life; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
C525984:(124)I-cMAb U36; D000911:Antibodies, Monoclonal; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals