Recombinant mouse/human chimeric monoclonal antibody A10 (ch‐A10) and its Fab fragment (ch‐Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I‐labeled ch‐Al0 and ch‐Fab in an antigen‐positive human pancreatic carcinoma (BxPC‐3) xenograft model. We also evaluated the anti‐tumor effect of 131I‐labeled ch‐Al0 and studied the detection of BxPC‐3 xenografts with 123I‐labeIed ch‐Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I‐labeled ch‐Al0 was significantly greater than that of 125I‐labeIed ch‐Fab 24 h post‐injection. However, the tumor‐to‐blood ratio was 46.8 for ch‐Fab at 24 h post‐injection, while it was only 1.4 for ch‐Al0. Microautoradiography studies showed that ch‐Fab penetrated more uniformly into the tumor nodules than did ch‐Al0. In mice given a therapeutic dose of 131I‐labeled ch‐AlO, a significant inhibition of tumor growth was seen, while control I31l‐labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I‐labeled ch‐Al0, but leukocyte counts recovered to normal levels at 8 weeks post‐injection. In whole‐body scintigraphy, clear and rapid tumor imaging was obtained with 200 (Ci of 123I‐labeled ch‐Fab 24 h post‐injection. These results suggest that radioiodine‐labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radio‐immunodetection of pancreatic carcinomas.
Fully depleted silicon on insulator (FD-SOI) MOSFET using low temperature sputtering SiO2 gate insulator (GI) was fabricated with resistless process without cleanroom and showed a characteristic comparable to that using plasma enhanced CVD. Resultant average characteristics with standard deviations were, field effect mobility µn of 612±37 cm2/Vs and subthreshold swing ss of 135±18 mV/dec. These were compared with our previous single crystal thin-film transistors (TFTs) on glass substrate with µn of 339±116 cm2/Vs and ss of 255±24 mV/dec, and it was cleared that inferior ss in TFTs was originated from bad bottom Si/SiO2 interface quality with a trap density of 1×1012 cm-2V-1. It was also shown that to achieve TFT characteristics the same as the FD-SOI-MOSFET, top interface trap density and bottom interface quality had better lower than 1×1011 cm-2V-1.
We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic-carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anticarcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo-oligomers (dimers and trimers) were prepared by linkage of chimeric Fab with N-succinimidyl-3-(2-pyridyldithio)-propionate. Oligomers with S-S bonds showed 10-fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab')2. In mice bearing pancreatic-carcinoma xenografts, tumor uptake of S-S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S-S Fab trimers and F(ab')2. S-S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab')2. At 18 hr after injection, clear scintigraphic detection of the pancreatic-carcinoma tumors was obtained with 123I-labeled S-S Fab dimers. At 24hr, improved tumor imaging was shown for 123I-labeled S-S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab')2. S-S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas.
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