Bispecific monoclonal antibody-mediated targeting of an indium-111-labeled DTPA dimer to primary colorectal tumors: pharmacokinetics, biodistribution, scintigraphy and immune response.
Eleven patients with primary colorectal carcinoma tumors (4 +/- 2 cm) were given intravenous injections of 1-10 mg of an anti-CEA, anti-In-DTPA bispecific Fab'-Fab monoclonal antibody, and 2-8 days later, were injected with 1.2-4.2 nmol of an 111In-labeled DTPA dimer (6 mCi). The bispecific antibody exhibited good stability and F(ab)'2-like pharmacokinetics. After injection, the 111In-DTPA dimer distributed in a large volume (88 ml/kg-180 ml/kg) and cleared through the kidneys (mean residence time in the whole body: 9 hr-16 hr). Uptake of 111In by the tumor using this two-step technique (1.8%-17.5% injected dose ID/kg, measured from surgical samples 48 hr after hapten injection) was not found significantly lower than that achieved with our reference 111In-labeled anti-CEA F(ab)'2 1 to 4 days after injection in six patients with similar clinical status (5.5%-30.2% ID/kg). In addition, tumor-to-blood and tumor-to-liver uptake ratios were significantly improved (blood 7.8 versus 4.2, liver 2.8 versus 0.8). As a result, low background images allowed detection of 12 of 13 lesions, 4 hr and 24 hr after hapten injection. However, 7 of 11 patients developed HAMA.
Le Doussal
J M
JM
Immunotech SA, Marseille, France.
Chetanneau
A
A
Gruaz-Guyon
A
A
Martin
M
M
Gautherot
E
E
Lehur
P A
PA
Chatal
J F
JF
Delaage
M
M
Barbet
J
J
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D018033:Antibodies, Bispecific / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D005260:Female; D006241:Haptens; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007205:Indium Radioisotopes / Q000276:immunology / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D004369:Pentetic Acid / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D004369:Pentetic Acid