Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in head and neck squamous cell carcinoma.
OBJECTIVE
In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo.


METHODS
Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36.


METHODS
In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only.


RESULTS
The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05).


CONCLUSIONS
The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.
Cheng
Junping
J
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Uppsala University Hospital (Akademiska Sjukhuset), Uppsala, Sweden.
Ekberg
Tomas
T
Engström
Mats
M
Nestor
Marika
M
Jensen
Holger J
HJ
Tolmachev
Vladimir
V
Anniko
Matti
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001246:Astatine / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000276:immunology / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects / Q000637:transplantation; D002465:Cell Movement; D020740:Chimerin Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D011897:Random Allocation; D013194:Staining and Labeling
D000911:Antibodies, Monoclonal; D020740:Chimerin Proteins; D001246:Astatine