No abstract

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value.

Fibrinogen was labeled with Tc-99m by two methods and in vitro stability and the in vivo behavior in mice were studied. The Tc-99m labeling was performed by mixing an unreduced fibrinogen (UnFib) or a reduced fibrinogen (ReFib) with Tc-99m pertechnetate in the presence of stannous chloride. In both of them, chelation with Tc-99m resulted in a single radiochemical product. For the in vitro stability studies, Tc-99m labeled fibrinogen (Tc-99m UnFib) was prepared with UnFib, and transchelation with cysteine solution was easy to produce compared to Tc-99m labeled fibrinogen (Tc-99m ReFib) prepared with ReFib. The radioactivity bound to clottable protein for Tc-99m UnFib and Tc-99m ReFib was about 70% and about 69%, respectively. The in vivo behavior of these labeled fibrinogens was studied, and their efficiencies for imaging an abscess and Ehrlich tumor in mice were determined with a gamma camera. Technetium-99m UnFib underwent a rapid partial exchange of the Tc-99m with compounds of the blood buffer system in vivo, resulting in early biologically active and would be incorporated into the abscess and tumor. The uptake in the abscess increased slightly over time with Tc-99m ReFib, but the abscess to blood and abscess to muscle ratios were 0.09 and 2.6 at 5 hr, respectively. Clearly delineated images of abscess were obtained beginning at about 5 hr after injection. The tumor to blood and tumor to muscle ratios were 0.05 and 1.4 at 5 hr, respectively. The Ehrlich tumor image in mice was slightly visible at 10 hr. The short half-life of Tc-99m was inappropriate for fibrinogen with a low pharmacokinetic value, because it was necessary for imaging of the abscess and tumor to take a long time.