Journal article
Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma.
- Storto G Department of Nuclear Medicine, University Hospital Lausanne, Switzerland. giosto24@hotmail.com
- Buchegger F
- Waibel R
- Kuenzi G
- Offord RE
- Schubiger PA
- Gillet M
- Delaloye AB
- 2002-01-05
Published in:
- Cancer biotherapy & radiopharmaceuticals. - 2001
Adenocarcinoma
Aged
Animals
Antibodies, Monoclonal
Antibodies, Neoplasm
Antigens, Neoplasm
Carcinoembryonic Antigen
Colorectal Neoplasms
Combined Modality Therapy
Female
Half-Life
Humans
Immunoconjugates
Immunoglobulin Fab Fragments
Iodine Radioisotopes
Liver Neoplasms
Male
Metabolic Clearance Rate
Mice
Middle Aged
Radioimmunodetection
Radioimmunotherapy
Tissue Distribution
English
UNLABELLED
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1089/108497801753354276
- PMID 11776754
- Persistent URL
- https://sonar.ch/global/documents/46096
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