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 -1 0 mg of an anti-CEA, anti-In -DTPA bispecific Fab'-Fab monoclonal antibody, and 2-8 days later, wer e injected with 1.2-4.2 nmol of an In-111-labeled DTPA dimer (6 mCi). The bispecific antibody exhibited good stability and F(ab)2'-like phar macokinetics. After injection, the In-111-DTPA dimer distributed in a large volume (88 ml/kg-180 ml/kg) and cleared through the kidneys (mea n residence time in the whole body: 9 hr-1 6 hr). Uptake of In-111 by the tumor using this two-step technique (1.80/,17.5% injected dose ID/ kg, measured from surgical samples 48 hr after hapten injection) was n ot found significantly lower than that achieved with our reference In- 111-labeled anti-CEA F(ab)2', 1 to 4 days after injection in six patie nts with similar clinical status (5.50/,30.2% ID/kg). In addition, tum or-to-blood and tumor-to-liver uptake ratios were significantly improv ed (blood 7.8 versus 4.2, liver 2.8 versus 0.8). As a result, low back ground images allowed detection of 12 of 13 lesions, 4 hr and 24 hr af ter hapten injection. However, 7 of 11 patients developed HAMA.