Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiolabeled antibodies have been studied by several investigators for their ability to detect and stage breast cancers. Studies with Technetium-99m labeled anti-CEA monoclonal antibodies, Iodine-123, Indium111 labeled anti-mucin antibodies such as HFMG, B72.3, anti-TF and Iodine-125 labeled B72-3 have demonstrated the ability of radioimmunoscintigraphy in detecting over 80% of breast cancer lesions, but lower sensitivity and specificity for accurate staging of the axillae. Non-specific localization of radiolabeled monoclonal antibodies in tumor negative nodes even following lymphoscintigraphy appear to be the major factor limiting the widespread clinical application of radioimmunoscintigraphy in staging newly diagnosed breast cancer patients. Preliminary studies with Tc-99m labeled CEA-Scan appear to indicate a useful role of this agent in distinguishing between benign and malignant breast lesions in patients with indeterminate mammographic findings.
...
PMID:Antibody imaging in breast cancer. 912 22

Anti-CEA-scintigraphy turned out very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90 p.c. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we lauched the following feasibility-study the results of which are compared to those reported in the recent literature. We investigated 20 patients-six with rectum-, 14 with colon cancer, 24 hours before surgery they were intravenously given 1 ml of an fab-fragment-antibody to CEA, labeled with 25mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regionary for the tumors was measured and compared to the-much lower-activity in healthy nodes. For this we used a scintillation-probe (C-Trak). All lymph nodes of interest were-then excised and submitted to frozen section pathology. In 7/20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regionary for the primary tumor. Our results are confirmed by those of other investigators. Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging when surgery is still on-going. In a next step the concept of sentinel-node-diagnosis, which is right now being clinically evaluated, may be applied is colorectal surgical oncology.
...
PMID:[Probe-guided surgery of colorectal carcinoma]. 927 9

Over the past 2 decades, numerous anticancer antibodies against different molecular targets and labeled with different gamma-emitting radionuclides have been studied in human tumor xenografts and in clinical trials. In breast cancer, these molecular targets have included principally tumor-associated antigens, such as carcinoembryonic antigen (CEA) and the polymorphic epithelial mucin antigen, MUC1, and more recently the growth factor receptors, EGF-R and HER-2/neu. No antibody-based agent has yet been approved for clinical use in the diagnosis of mammary carcinoma, because few trials have addressed the issue of clinical use of these imaging agents in the management of breast cancer patients. Recently, the CEA antibody Fab' fragment approved for colorectal cancer detection, Arcitumomab (CEA-Scan, [Immunomedics, Morris Plains, NJ]), has been found to image both palpable and nonpalpable breast lesions that were suspicious on screening mammograms. Results to date indicate that Arcitumomab can complement mammography by providing a high specificity and positive predictive value, thus indicating when a patient with an abnormal mammogram may proceed directly to definitive surgery without an intermediate diagnostic biopsy. Breast cancer immunoscintigraphy holds promise for advancing toward immunoPET, which should combine the specificity of antibodies with the high sensitivity and resolution of PET. It is also the foundation of breast cancer radioimmunotherapy with humanized antibodies against CEA and MUC1, as well as other immunotherapy strategies.
...
PMID:Breast cancer imaging with radiolabeled antibodies. 999 Jun 82

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.
...
PMID:A thousand points of light or just dim bulbs? Radiolabeled antibodies and colorectal cancer imaging. 1037 Mar 60

The goal of this work was to test whether an antibody-based agent approved for use as a single-photon-emitting imaging agent when radiolabeled with technetium-99m could be labeled comparably with a positron-emitting nuclide, technetium-94m. "Instant kits" containing lyophilized NP-4 antibody Fab' fragment of an anticarcinoembryonic antigen IgG (CEA-Scan) from the same manufactured lot were reconstituted with either Tc-99m or Tc-94m, as solutions of sodium pertechnetate in isotonic saline solution. Radioanalyses of the labeled Fab' fragments by size-exclusion high-performance chromatography and TLC were carried out. Equivalent results were obtained for radioimmunoconjugates when each was analyzed with both methods. Facile incorporation of Tc-94m into tumor-targeting Fab' antibody fragments will enable investigation of such agents for tumor-specific imaging using positron emission tomography.
...
PMID:Radiolabeling of an anti-carcinoembryonic antigen antibody Fab' fragment (CEA-Scan) with the positron-emitting radionuclide Tc-94m. 1054 34

Anti-CEA-scintigraphy turned out to be very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90%. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we launched the following feasibility study the results of which are compared to those reported in the recent literature. We investigated 20 patients, six with rectum and 14 with colon cancer. 24 hours before surgery they were intravenously given 1 ml of a fab'-fragment-antibody to CEA, labeled with 25 mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regional to the tumors was measured and compared to the much lower activity in healthy nodes. For this we used a scintillation probe (C-Trak, Care Wise, Inc., Morgan Hill, CA). All lymph nodes of interest were then excised and submitted to frozen section pathology. In 7 out of 20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regional to the primary tumor (retroperitoneum, renal hilum etc.). Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging while surgery is still ongoing. In a further step the concept of sentinel node diagnosis, which is right now being clinically evaluated, may some day be applied in colorectal surgical oncology.
...
PMID:Probe-guided surgery for colorectal cancer. 1085 80

Carcinoembryonic antigen (CEA), highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET]) have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab', scFv, minibody, diabody and scFv-Fc) have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a (99m)Tc-labeled anti-CEA Fab' fragment) has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. (18)F and (99m)Tc) are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. (123)I and (111)In) are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to "personalized medicine".
...
PMID:Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen. 1957 24

Imaging of cancer by radioimmunoscintigraphy (RIS) following administration of radiolabeled monoclonal antibodies (mAbs) or fragments has been under development for two decades. Efficacy is a function of many variables: antigen expression on tumor cells relative to normal tissues and body fluids, affinity, specificity, pharmacokinetics and immunogenicity of the mAb and properties of the radionuclide and imaging techniques. CEA-Scan (a 99mTclabeled Fab' fragment of a mouse mAb directed against CEA) has several advantageous properties, and has been approved for use in colorectal cancer SPECT imaging in North America and Europe, and is also under investigation in Japan. It has been shown to complement CT in detecting recurrent or metastatic disease, even in the liver where 111In mAbs frequently fail. In breast cancer, it provides clearer identification of malignant disease in patients with indiscriminate mammography. Recently, it has also been used intra-operatively in radio-immunoguided surgery in both colorectal and breast cancer patients. These new applications are currently under active investigation and clinical trials are planned. Clinically useful information is obtained in a relatively high percentage of patients, which can alter treatment decisions. In most cases the benefits are in reducing unnecessary surgery or biopsies in inoperable patients, but major benefits (especially in colorectal cancer) would be obtained if new therapies effective against the RIS-detected minimal residual disease were forthcoming.
...
PMID:Technology evaluation: CEA-Scan, Immunomedics Inc. 1962 71