Anti-CEA and Other Antibodies in the Study of Gastrointestinal Tumors (original) (raw)
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Radiology, 1990
Metastatic colorectal cancer was detected with stabilized F(ab')2 fragments of ZCE-025, an anti-carcinoembryonic antigen (CEA) monoclonal antibody (MoAb). The fragments were prepared by cross-linking Fab' with a bifunctional cross-linking agent, bis-(maleimido)methyl ether. The authors labeled 2 mg of ZCE-025 with 5 mCi (185 MBq) of mdium-lil and injected the material intravenously, either alone or with unlabeled F(ab') , into 16 patients. Lesion detection, pharmacokinetics, and relative body distribution were evaluated and compared with those of the intact immunoglobulin (IgG1) antibody. Stabilized F(ab')2 fragments were more useful than the intact antibody in detection of lesions: Overall sensitivity of F(ab')2 fragments for all the patients was 79.4%, whereas overall sensitivity of the intact IgG1 antibody was 32%. This anti-CEA-stabilized F(ab')2 fragment may be a powerful diagnostic tool that can achieve higher sensitivity at smaller protein doses than the intact IgG1 antibody.
Tumor Localization in Patients by Radiolabeled Monoclonal Antibodies against Colon Carcinoma1
2000
A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorec- tal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma pa tients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumu
Nuclear Medicine and Biology, 2009
Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anticarcinoembryonic antigen antibody ([ 125 I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [ 131 I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., ∼15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., ∼80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6±12.9 vs. treated mean survival of 39.1±30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology, 1991
Tumour-to-normal tissue ratios of i.p. injected 125I-labelled monoclonal antibodies (MAbs), reacting with CEA were determined in nude rats xenografted with human colonic cancer cells (LS 174 T). Two MAbs, I-38S1 and II-16, reactive with the GOLD 1-epitope on CEA were tested. MAb I-38S1 was also tested after additional purification using anion exchange chromatography (thereafter named AEC 38). In the external activity measurements, MAb AEC 38 showed significantly better tumour-to-liver ratios than did MAb II-16 on all 4 days after injection. MAb I-38S1 gave intermediate ratios but was significantly better than II-16 only on day 3. The mean tumour-to-blood ratios were 3.0, 2.6 and 1.5 and the mean tumour-to-liver ratios were 6.6, 4.8 and 3.5 for MAbs AEC 38, I-38S1 and II-16 respectively. Gamma camera registrations in 3 animals on 4 days showed good imaging properties for all three MAbs and the patterns of tissue uptake were consistent with those seen in the external measurements. Fur...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1992
Previous experimental results in nude mice showing that radiolabeling the monoclonal antibody anti-CEA 35 with 67Ga-aminooxyacetyldeferroxamine could give better tumor localization than radioiodination prompted us to initiate the present clinical study. The 67Ga-labeled antibody anti-CEA 35 (185 MBq, 0.7-1.7 mg) was injected preoperatively into 14 patients for colorectal carcinoma imaging. The same antibody labeled with 125I (3.7 MBq, 0.25 mg) was injected simultaneously to compare the 67Ga and 125I dose recoveries in surgical specimens. Twelve of 14 primary tumors gave a positive 67Ga scintigraph. The mean %ID/g recovered in all tumors 3-9 days after injection was significantly higher for 67Ga (0.019%) than for 125I (0.005%) (p < 0.001, paired t test). The tumor-to-normal tissue ratios were generally higher for 67Ga, with the exception of liver. We conclude that 67Ga-aminooxyacetyldeferroxamine improved immunoscintigraphy outside the liver, particularly in the pelvic region. We ...
European Journal of Cancer and Clinical Oncology, 1991
Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Turnout localisation was carried out with 185 MBq 1311-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy was positive in at least one organ site with disease. Of all sites, 55% could be visualised. In general, lesions < 3 cm could not be detected. Sequential immunoscintigrams of liver metastases showed variable patterns. Initial "cold" lesions corresponded to liver metastases with poor blood supply as indicated by 99mTc-sulphur-colloid and 99mTc-HMPA0 scintigraphy, respectively. The mean (S.D.) biological half-life (whole body clearance of radioactivity) was 37.6 (5.0) h. A second infusion of 13'1-16.88 with the addition of high doses of unlabelled 16.88 could be done safely, but did not result in better visualisation of turnout lesions or affect radioactivity clearance from the body.
Clinical Oncology, 1992
Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using H~In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of HIIn-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients. Our comparative study (performed blind) supports the main role of immunoscintigraphy with fragments of anti-CEA monoclonal antibodies in the early detection of extrahepatic recurrences of Correspondence and offprint requests to: gastrointestinal carcinomas in both CEA seropositive and seronegative patients.