Biokinetics of a F(ab′) 3 Iodine-131 Labeled Antigen Binding Construct (MAb 35) Directed Against CEA in Patients with Colorectal Carcinoma

Abstract

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 (5M,1F; 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 αT1/2 of 6.3 ± 1 h and βT1/2 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.