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Titolo:
TUMOR-DETECTION WITH I-131-LABELED HUMAN MONOCLONAL-ANTIBODY COU-1 INPATIENTS WITH SUSPECTED COLORECTAL-CARCINOMA
Autore:
DITZEL H; RASMUSSEN JW; ERB K; BORUPCHRISTENSEN P; TITLESTAD I; LASSEN E; FENGER C; KRONBORG O; JENSENIUS JC;
Indirizzi:
SCRIPPS CLIN & RES INST,DEPT IMMUNOL IMM2,10666 N TERREY PINES RD LA JOLLA CA 92037 ODENSE UNIV,DEPT MED MICROBIOL DK-5230 ODENSE DENMARK ODENSE UNIV HOSP,DEPT NUCL MED DK-5000 ODENSE DENMARK ODENSE UNIV HOSP,DEPT SURG DK-5000 ODENSE DENMARK ODENSE UNIV HOSP,DEPT PATHOL DK-5000 ODENSE DENMARK AARHUS UNIV,INST MED MICROBIOL DK-8000 AARHUS DENMARK
Titolo Testata:
Cancer research
fascicolo: 24, volume: 53, anno: 1993,
pagine: 5920 - 5928
SICI:
0008-5472(1993)53:24<5920:TWIHMC>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HYBRIDOMAS; IMMUNE-RESPONSE; CANCER-PATIENTS; LOCALIZATION; ANTIGENS; QUANTITATION; INJECTION; FRAGMENTS; THERAPY; SURFACE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
H. Ditzel et al., "TUMOR-DETECTION WITH I-131-LABELED HUMAN MONOCLONAL-ANTIBODY COU-1 INPATIENTS WITH SUSPECTED COLORECTAL-CARCINOMA", Cancer research, 53(24), 1993, pp. 5920-5928

Abstract

A major factor limiting the use of rodent monoclonal antibodies for diagnosis and therapy of cancer is the development of human anti-mouse immunoglobulin antibodies. Here we report a phase I/II immunodetectionstudy of a human monoclonal antibody, COU-1, labeled with I-131. COU-1 is produced by a human-human hybridoma and recognizes a M(r) 43,000 cytokeratin-like protein strongly expressed by adenocarcinomas of the colon, breast, and ovary. Ten patients were given an i.v. infusion of 2 mg of antibody COU-1 labeled with 185 MBq of I-131. No adverse effects or toxicity were detected by conventional clinical tests nor by a complement activation assay for C3d. None of the patients developed antibodies against antibody COU-1 as determined by enzyme-linked immunosorbent assay and agglutination analysis. Tumor detection was successfulin 7 of 9 cancer patients. The tenth patient proved to be a true negative. In several instances immunoscintigraphy gave additional or more correct information than conventional detection techniques. Tumors were most clearly outlined at days 5 and 7 after infusion. Primary colorectal carcinomas were detected by planar imaging in the cecum, ascending colon, and rectum with the smallest lesion measuring 3.0 cm in diameter. Immunoscintigraphy revealed multiple liver metastases in 1 of 3 patients. However, the livers of all 3 patients contained significantlymore radioactivity (P < 0.005) than tumor-free livers of the other patients. Pharmacokinetics was evaluated in all patients. The clearance of I-131-labeled COU-1 from the circulation followed a triphasic pattern; an initial phase [t1/2 = 0.4 +/- 0.4 (SD) h] cleared 23% of the radioactivity followed by a rapid phase with a half-life of 13 +/- 3.8 h. The third phase (beta-phase) exhibited a half-life of 119 +/- 36 h, which is similar to the half-life reported for normal IgM. The human monoclonal antibody COU-1 directed against a predominantly intracellular cancer-associated antigen does not produce toxicity or induce antibody formation and seems to be a promising agent for detecting tumors with immunoscintigraphy.

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Documento generato il 24/09/20 alle ore 08:25:24