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Single chain antigen binding protein (sFv CC49)
Author(s) -
Larson Steven M.,
ElShirbiny Ayda M.,
Divgi Chaitanya R.,
Sgouros George,
Finn Ronald D.,
Tschmelitsch Jorg,
Picon Antonio,
Whitlow Marc,
Schlom Jeffrey,
Zhang Jiaju,
Cohen Alfred M.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2458::aid-cncr17>3.0.co;2-b
Subject(s) - medicine , clearance , parenchyma , spleen , distribution (mathematics) , kidney , biodistribution , excretion , nuclear medicine , pathology , monoclonal antibody , extracellular fluid , whole body imaging , antibody , extracellular , urology , positron emission tomography , chemistry , immunology , biochemistry , mathematical analysis , mathematics , in vitro
BACKGROUND An sFv fragment of the anti‐TAG‐72 monoclonal antibody CC49 has been developed and has shown promise in improved targeting to colorectal carcinoma in animal studies. In this study the authors report their initial experience in human patients after intravenous injection. METHODS Five patients with colorectal carcinoma metastatic to the liver were studied prior to surgery. High performance liquid chromatography showed a low level of aggregation (< 10% complex formation), before and after radiolabeling with iodogen. Prior to radiolabeling, 123 I was brought to the dry form, phosphate buffer added and titrated to a pH of 7, with diluted hydrochloric acid. 123 I was injected in doses of 26, 12, 27, 25 and 1 millicurie, respectively, and labeled to a 5‐mg fragment. Single photon emission computed tomography and whole body imaging were performed at 4‐6 hours, and 24 hours, respectively, after injection. RESULTS The agent was rapidly cleared from the blood with biphasic clearance T‐1/2 of 30 minutes and 10.5 hours, respectively. Distribution from whole body imaging confirmed rapid equilibration with extracellular fluid, and clearance T‐1/2 from the body was comparable to the slower component of blood clearance. The spleen was visualized in all patients, and the testes were imaged in 67% of male patients. Renal excretion was noted with early uptake and clearance from the renal parenchyma except in one patient in whom renal parenchyma retention was intense. Although image quality was suboptimal, tumor was visualized in all five patients in both primary and metastatic lesions. At surgery, (16‐24 hours postinjection), the tumor retained significant concentrations of the radiotracer, with metastatic tumor/normal liver ratios of approximately 1:5‐3:1. No patient had any associated symptom or change in biochemical and hematopoietic status. CONCLUSIONS This study showed that sFv is safe, tissue equilibration and clearance is rapid, and early, same‐day imaging of the primary and metastatic tumors is feasible in patients colorectal carcinoma. Further studies are warranted to define a more optimal mass of sFv CC49 dose for tumor targeting. Cancer 1997; 80:2458‐68. © 1997 American Cancer Society.