Efficient targeting of gastric cancer cells using radiolabeled anti-carcinoembryonic antigen-specific T84.66 fragments in experimental radioimmunoguided surgery.
BACKGROUND
Radioimmunoguided surgery (RIGS) appears as an efficient tool for accurate tumor detection up to the level of micrometastases by detecting radiolabeled antibody-bound tumor cells during operation. Anti-CEA-specific T84.66 fragments were examined as to whether they efficiently detected gastric cancer cells in experimental RIGS. T84.66, anti-CEA-specific antibody, has widely been used as an immune carrier in the preclinical and clinical trials of radioimmunotherapy and radioimmunoscintiscan.


METHODS
Fifty-one tumors from two human gastric carcinoma cell lines with profuse (MKN45) and low (RF48) CEA expression were successfully implanted subcutaneously in the backs of 32 nude mice. Tumors were localized after 125I-labeled T84.66 F(ab')2 and Fab' injection.


RESULTS
The radioactivity of F(ab')2-pretreated mice was greater than that of Fab'-pretreated in all organs and tumors (p<0.001-0.035). Localization indices of the tumor in various organs revealed 7.4 to 32.5 in F(ab')2-pretreated and 1 to 7.1 in Fab'-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells regardless of fragment types and cell lines. There was no false-negative evaluation of tumor in F(ab')2-pretreated mice. Sensitivity and specificity of tumor localization by RIGS were the highest in the F(ab')2-pretreated mice (95% for MKN45- and 82% for RF46-xenografted mice) and the least in the Fab'-pretreated mice (66% for MKN45- and 67% for RF46-xenografted mice). In all organs, three quarters of the false-positive evaluations occurred from silver grains as radioimmune complex or dissociated nuclides in the circulation that can be eliminated with time.


CONCLUSIONS
Anti-CEA-specific T84.66 fragments achieved a great affinity and avidity with accurate localization of gastric carcinoma in experimental RIGS.
Kim
Jin C
JC
Department of Surgery, University of Ulsan College of Medicine and Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Seoul, Korea. jckim@amc.seoul.kr
Hong
Hyun K
HK
Roh
Seon A
SA
Koo
Kum H
KH
Ka
In H
IH
Namgung
Hwan
H
Lee
Kang H
KH
Ryu
Jang H
JH
Yu
Chang S
CS
Oh
Seung J
SJ
Ryu
Jin S
JS
Kim
Jung S
JS
Kim
Hee C
HC
D000818:Animals; D001345:Autoradiography; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use*; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000378:metabolism; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D011877:Radionuclide Imaging; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D023041:Xenograft Model Antitumor Assays
D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes