Bispecific Monoclonal Antibody-Mediated Targeting of an Indium-111-Labeled DTPA Dimer to Primary Colorectal Tumors: Pharmacokinetics , Biodistribution, Scintigraphy and Immune Response

• Published in: The Journal of nuclear medicine (1978) Vol. 34; no. 10; pp. 1662 - 1671
• Main Authors: Le Doussal, Jean-Marc, Chetanneau, Alain, Gruaz-Guyon, Anne, Martin, Marie, Gautherot, Emmanuel, Lehur, Paul-Antoine, Chatal, Jean-Francois, Delaage, Michel, Barbet, Jacques
• Format: Journal Article
• Language: English
• Published: United States Soc Nuclear Med 01.10.1993
• Subjects: Adenocarcinoma - diagnostic imaging; Adenocarcinoma - immunology; Aged; Aged, 80 and over; Antibodies, Bispecific - immunology; Antibodies, Monoclonal - immunology; Colorectal Neoplasms - diagnostic imaging; Colorectal Neoplasms - immunology; Female; Haptens; Humans; Immunoglobulin Fab Fragments - immunology; Indium Radioisotopes - immunology; Indium Radioisotopes - pharmacokinetics; Male; Middle Aged; Pentetic Acid - pharmacokinetics; Radionuclide Imaging; Sensitivity and Specificity; Tissue Distribution
• ISSN: 0161-5505; 1535-5667

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.