Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery

Kim, Jin C.; Roh, Seon Ae; Koo, Kum H.; Ryu, Jang H.; Hong, Hyun K.; Oh, Seung Jun; Ryu, Jin Suk; Kim, Ho J.; Bodmer, W F

doi:10.1002/ijc.1630

Cited by 10 publications

(13 citation statements)

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“…Radionuclides most suitable for RIGS should emit radiation with little penetration and have a suffi ciently long half-life to allow blood clearance of radioactivity obtaining the elevated tumor-to-blood ratio [17] . The ␥ -emitting radionuclide, 125 I, corresponds best to these prerequisites, and the iodogen method used in this study was shown to produce a stable attachment of radiochelate to antibody, thus resulting in a strong conjugate [15,18] . Although several investigations of immunoscintiscan showed accurate imaging using 99m Tc, the mismatch in the half-life of 99m Tc and antibody is too great to effi ciently localize tumors [5] .…”

Section: Discussionmentioning

confidence: 99%

“…Anti-CEA antibodies tend to clear swiftly from the non-specifi c background and both biparatopic and its parental antibodies effi ciently targeted tumor CEA in our previous studies [15,16] . Radionuclides most suitable for RIGS should emit radiation with little penetration and have a suffi ciently long half-life to allow blood clearance of radioactivity obtaining the elevated tumor-to-blood ratio [17] .…”

Section: Discussionmentioning

confidence: 99%

“…The biparatopic antibody was prepared using cross-linking of reduced Fab fragments of two antibodies according to a method previously used [15] . Briefl y, reduced Fab fragments were concentrated to 5 mg/ml in a 50-m M sodium acetate buffer using a microconcentrator.…”

Section: Construction Of Biparatopic Antibodymentioning

confidence: 99%

“…Therefore, biparatopic or multiparatopic antibodies directed to different epitopes of the same molecule have been tried to overcome these steric hindrances [14] . Biparatopic antibodies using several combinations of antibodies against CEA gave greater tumor uptake and less normal tissue retention than that of the unmodifi ed fragments [7,15] .…”

mentioning

confidence: 99%

“…This preclinical RIGS was intended to test the effi cacy and possible clinical applicability of the biparatopic antibody, as shown with accurate localization of colorectal cancer cells in our preceding animal study [15] . The biparatopic antibody was designed using two anti-CEAspecifi c antibodies, T84.66 and PR1A3, reacting against two different epitopes.…”

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confidence: 99%

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Preclinical Application of Radioimmunoguided Surgery Using Anti-Carcinoembryonic Antigen Biparatopic Antibody in the Colon Cancer

Kim

Roh²,

Koo³

et al. 2005

Eur Surg Res

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Radioimmunoguided surgery (RIGS) has been known as a sophisticated tool to detect micrometastasis intraoperatively. A preclinical model of RIGS was designed to test the possible clinical applicability of the biparatopic antibody in detecting colorectal cancer. The biparatopic antibody was constructed using two anti-carcinoembryonic antigen (CEA)-specific antibodies, T84.66 and PR1A3, reacting against two different epitopes. ¹²⁵I-labeled biparatopic antibody was introduced via the principal colonic arteries at the end of operation in 10 operable patients with colon cancer. After 24 h, the radioactivities of the tumors and lymph nodes were counted using the γ-detecting probe. The radioactivity count was performed ex vivo. The accurate detection in the primary tumors and metastatic lymph nodes were 100 and 88.7% respectively. False-positive detections occurred in 24 of 256 lymph nodes (9.4%), whereas false-negative detections occurred in 5 of them (2%). The most frequent cause of false-positive detection was dissociated radionuclides trapped in the lymphatic tissues. False-negative detections occurred mainly from weak targeting by radiolabeled antibody, probably due to weak expression of tumor CEA. Conclusively, as most detection errors appear to be reduced within 3 days in vivo, the biparatopic antibody can efficiently be applied to the clinical RIGS, thereby facilitating accurate detection and removal of occult cancer foci in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Construction Of Biparatopic Antibodymentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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