Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium-diethylenetriaminepentaacetic acid (Gd-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-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-DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of GdDTPA-mAb 19-9 (Gd, 20 pumol/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 GdDTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 jsmol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for GdDTPA (10-100 j#mol/kg) as contrast agent. Tumor localiztion by the Gd-DTPA-mAb 19-9 complex containing radioactive Gd (0.3 IACi/tg of ls3Gd) 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.Nuclear magnetic resonance (NMR) proton imaging provides sharp contrast between tissues based on their intrinsic T1 and T2 relaxation times when varied pulse sequences are used. By exploiting the differences in relaxation times, images have been produced that provide previously unobtainable anatomic and physiologic information. Early investigators felt that differences in relaxation times between tumors and normal tissue made contrast agents unnecessary. However, despite this intrinsic tissue contrast, the absence of oral or intravenous contrast agents has proved disadvantageous (1, 2). Various intravenous and oral contrast agents have been proposed, including paramagnetic metal ions and their chelates and complexes (3, 4). Recently, attention has focused on gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), a complex that produces a marked reduction in the proton relaxation ratio in vitro and in vivo and appears to have minimal acute toxicity in imaging doses (5, 6). One approach to increasing the specificity of NMR image contrast is to use paramagnetic contrast agents coupled with a monoclonal
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