Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

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Abstract
Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium .cntdot. diethylenetriaminepentaacetic acid (Gd .cntdot. DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd .cntdot. DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd .cntdot. DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd .cntdot. DTPA-mAb 19-9 (Gd, 20 .mu.mol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd .cntdot. DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 .mu.mol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd .cntdot. DTPA (10-100 .mu.mol/kg) as contrast agent. Tumor localization by the Gd .cntdot. DTPA-mAb 19-9 complex containing radioactive Gd (0.3 .mu.Ci/.mu.g of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors.