Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma.
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.


OBJECTIVE
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.


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.
Storto
G
G
Department of Nuclear Medicine, University Hospital Lausanne, Switzerland. giosto24@hotmail.com
Buchegger
F
F
Waibel
R
R
Kuenzi
G
G
Offord
R E
RE
Schubiger
P A
PA
Gillet
M
M
Delaloye
A B
AB
D000230:Adenocarcinoma / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000097:blood / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008875:Middle Aged; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes