Article: article from journal or magazin.
Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma.
Cancer Biotherapy & [and] Radiopharmaceuticals
An 131I labeled trivalent antigen binding construct, formed from 3 Fab' fragments of murine anti-CEA monoclonal antibody (Mab) 35, has shown favorable biokinetics in animal studies. OBJECTIVES: The aim of this study was to evaluate biodistribution and tumor uptake of 131I-F(ab')3 in patients and its potential utility for radioimmunotherapy of CEA expressing tumors. PATIENTS AND METHODS: Six patients (5 M, 1 F; age 62 +/- 13 y) with liver metastases of colorectal cancer, scheduled for hepatic surgery were studied by 2-3 whole body scans immediately post infusion of 111-137 MBq of 131I labeled Mab 35 F(ab')3 and up to 72 h. Circulating CEA ranged from 1.2 to 1930 ng/ml. We evaluated plasma and whole body clearance, activity accumulation by post-surgical ex-vivo tissue measurement in primary tumor (T) and metastases (M), and calculated M to blood (M/B) and M to liver (M/L) ratios. RESULTS: All known tumor sites were detected by immunoscintigraphy and confirmed at surgery. Whole body effective T1/2 calculated in two patients was 51.5 h and 55.6 h respectively. Effective serum T1/2 was mono-exponential in 3 patients (short observation interval) with 20.9 +/- 7 h and bi-exponential in three with alpha T1/2 of 6.3 +/- 1 h and beta T1/2 of 38.6 +/- 5 h. In a patient with concomitant colic and hepatic lesions uptake of primary tumor was 0.0071% injected dose per gram of tissue (%ID/g) and mean metastases activity was 0.0275 %ID/g at 48 h. In the 3 patients who had surgery at 48 h, mean uptake in metastases and normal liver was 0.0182 %ID/g and 0.0021 %ID/g, respectively (M/L 8.67). In the single subject followed until 7 days post infusion, residual activity in liver metastases was 10 times higher than in normal parenchyma. CONCLUSIONS: Tumor uptake and tumor to blood ratio, as well as serum clearance of the triconstruct are similar to those observed with intact iodinated anti-CEA antibodies. In the patient studied for 7 days the tumor residence time was favorable. Further improvements, however, need to be obtained before considering this approach for radioimmunotherapy.
Adenocarcinoma/blood, Adenocarcinoma/immunology, Adenocarcinoma, Aged, Animals, Antibodies, Monoclonal/blood, Antibodies, Monoclonal/diagnostic use, Antibodies, Neoplasm/blood, Antibodies, Neoplasm/diagnostic use, Antigens, Neoplasm/immunology, Carcinoembryonic Antigen/immunology, Colorectal Neoplasms/blood, Colorectal Neoplasms/immunology, Combined Modality Therapy, Female, Half-Life, Humans, Immunoconjugates/therapeutic use, Immunoglobulin Fab Fragments/blood, Immunoglobulin Fab Fragments/diagnostic use, Iodine Radioisotopes/blood, Iodine Radioisotopes/diagnostic use, Liver Neoplasms/blood, Liver Neoplasms/immunology, Liver Neoplasms, Male, Metabolic Clearance Rate, Mice, Middle Aged, Radioimmunodetection, Radioimmunotherapy, Tissue Distribution
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