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PubMedDate not supplied

Radioimaging of experimental glioma grafts using F (ab')2-fragments of monoclonal antibodies.

Iodinated F (ab')2-fragments of monoclonal IgG2a-antibodies (McAbs) 14 AC1 raised against membrane components of an experimental rat glioma (79FR-G-41) were used for the radioimmunodetection of glioma xenografts in athymic mice. For gamma imaging, nude mice with intramuscular glioma grafts received 10-20 micrograms of 131I-labelled whole immunoglobulins and F (ab')2-fragments of the 14AC1 McAb, respectively, with an activity of 50-150 mu Ci (1.85-5.55 MBq). Scans obtained at 24, 48, 72 and 96 hours after injection demonstrated tumor accumulation of F (ab')2-fragments at 24 hours, and adequate tumor visualization without background subtraction at 48 hours. The rapid blood clearance of F (ab')2-fragments resulted in a whole body half life of 6 hours. Scintigrams using intact antibody provided comparable tumor localization at 96 hours, but also high bloodpool radioactivity and a half life period of more than 4 days. 131I-labelled normal mouse-IgG as control for non-specific uptake of immunoglobulins in the tumor revealed no tumor visualization at any time. Rapid tumor permeation, short blood clearance and a markedly reduced background radioactivity let F (ab')2-fragments appear superior to whole immunoglobulins in immunoscintigraphy, thus indicating their potential value for the improvement of radioimmunodiagnosis of glioma disease.

Animals↗
PubMed1985

Localization of radiolabeled monoclonal antibody in a human soft tissue sarcoma xenograft.

125I-labeled monoclonal antibody 19-24 (mouse isotype IgG1) was evaluated for its potential usefulness in the clinical radioimmunodetection of sarcoma. The antibody reacts with a cell surface antigen preferentially expressed in many human soft tissue and bone sarcomas. Chromatographic and electrophoretic analyses indicated that the labeled preparation was relatively pure. Binding studies in vitro demonstrated that specificity for antigen was retained after iodination and indicated that the labeled antibody possessed an immunoreactivity in excess of 90% and a binding constant of 8.1 X 10(9) M-1. When administered to athymic NCr-nu/nu mice bearing 1-cm diameter human fibrosarcoma HT-1080 xenografts, the labeled antibody preferentially localized in tumor deposits. Maximum tumor-to-blood radioactivity ratios (2.2-3.4) were obtained 7 days after antibody injection. Specificity of the localization was confirmed with a control mouse IgG1 antibody and by using a nonreactive xenograft. Distinct tumor images were obtained by gamma camera without the use of subtraction techniques, demonstrating the possible clinical utility of the labeled antibody.

Animals↗
PubMed1985

[Analysis of cell surface antigens of gastric cancer and preliminary study of clinical application by using mouse monoclonal antibodies produced against NUGC3].

Four monoclonal antibodies (GC301, 302, 303, 304) produced by hybridomas obtained from mice immunized with NUGC3 were analyzed by serological assay (Mixed Hemadsorption Assay-MHA) and immunoperoxidase technique. GC301(IgG1) showed tumor restricted reactivity in serological analysis, but it reacted with fibrous interstitial tissues immunohistochemically. GC302(IgG1) was serologically reactive with epithelial tumors such as gastric cancers, colon cancers and gynecological cancers, but not with brain tumors, melanomas and other normal cells. In tissue sections, all gastric cancers, intestinal metaplasia, stomach of fetus and bile duct were stained, but brain and hepatocytes were not. These results indicate that the antigen detected by GC302 is not only differentiation antigen by which gastrointestinal tract could be divided into foregut and midgut origins, but also the new type of oncofetal antigen different from CEA. GC302 would be useful for preoperative detection of gastric cancer in lymph nodes, using radioimmunodetection scans. GC303(IgG1) and GC304(IgG1) were broadly reactive with various cells in serological assay. Immunohistochemically, GC304 reacted with submucosal connective tissue, which was inhibited by collagenase. The results obtained from GC301 and GC304 suggest the possibility of interaction between tumor cells and interstitial tissues.

Aged↗
PubMed1986

Quantitative whole-body autoradiography of radiolabeled antibody distribution in a xenografted human cancer model.

Quantitative whole-body autoradiography (WBAR) was used to study the biodistribution of goat anti-carcinoembryonic antigen and normal goat IgG, each labeled with 125I, in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma xenograft. Comparisons between computer-assisted videodensitometric profiles of WBARs and tissue radioactivity counts were made at 1, 3, and 7 days following administration of the radiolabeled IgGs. The results indicated that maximal tumor accretion of the radiolabeled antibody and normal IgG occurred within 1-3 days, with a marked selective accretion of antibody in the tumor being evidenced at 3-7 days because of clearance of normal IgG. Radioactivity derived from antibody IgG showed 6.5 to 118.7 times that found in other tissues, as measured by videodensitometry, whereas organ radioactivity counting revealed ratios of only 6.7 to 29.6. Specificity of tumor-cell accretion of the radiolabeled antibody was confirmed by microscopic autoradiography, showing intense labeling of the proliferating perimeters of GW-39 tumors. WBAR was found to have a resolution of 0.10 to 0.25 mm in 100-g hamsters, which appears to be greater than the resolving power of external body imaging by gamma camera scintigraphy. These studies suggest the use of WBAR and microautoradiography to complement external imaging methods for the analysis of antibody distribution and localization in cancer radioimmunodetection models.

Animals↗
PubMed1983

Hormones as tumor markers.

At present, hormones are clinically useful markers only for a minority of tumors, but in certain cases they are important for the diagnosis as well as for the follow-up of patients after treatment. In the future their application as tumor markers may be expanded by the use of methods such as radioimmunodetection and the study of hormone precursors and fragments.

Chorionic Gonadotropin↗
PubMed1983

[Application of anti-AFP monoclonal antibodies to diagnosis].

Twenty-two hybridoma clones which produced monoclonal antibodies to human alpha-fetoprotein (AFP) were established by the fusion of myeloma cells and spleen cells of mice immunized with AFP. Hybridomas were transplanted i.p. and antibodies were purified from the ascites of tumor-bearing mice. Antibodies were used for the purification of AFP by immuno-affinity chromatography and increased amounts of AFP were isolated in higher yields. Antibodies were used in the AFP radioimmunoassays and successful result was obtained when used in the sandwich technique. Antibodies were also tested in the radioimmunodetection of AFP-producing tumors and positive images of tumors were obtained in several cases.

Animals↗
PubMed1983

Localizing properties of antibody to alphafetoprotein (AFP) to AFP-producing tumor cells.

Studies have been undertaken to clarify the localizing properties of radioactively labeled antibody to AFP using ascitic hepatoma cells which produce AFP. In the in vitro studies, radioantibodies to AFP were incorporated into the AFP-producing cells, even though excess antigen existed in the medium and the antibodies remained on the cell surface for a long time. In the in vivo studies, the radioantibodies to AFP bound to the AFP-producing cells, especially those producing high levels of AFP (AH66). Tumor localization by scintigraphy was clearer with the AH66 hepatoma than with the AH41C hepatoma, which produces less AFP. The presence of large amounts of AFP in the circulation did not prevent the tumor radioimmunodetection. It is suggested that radioantibodies to AFP bind to the AFP-producing cells despite the presence of large amounts of AFP in the circulation or in ascitic fluid.

Animals↗
PubMed1984

Tumorigenicity in athymic mice of the human colon carcinoma cell line SW1116 expressing the tumor-associated antigenic determinant CA 19-9.

The human colorectal carcinoma cell line SW1116 under optimal growth conditions synthesized and shed antigens bearing the monoclonal antibody-defined carbohydrate determinant CA 19-9. Antigen expressing CA 19-9 in cell culture supernatant was quantitated by an immunoradiometric assay for CA 19-9. Injection of SW1116 cells s.c. into athymic BALB/c mice resulted in the growth of moderately differentiated tumors possessing a distinct morphological resemblance to a typical adenocarcinoma of the colon. Intervals to tumor appearance were dependent on inoculum dose, but 95% of mice at both 5 X 10(6) and 10(7) cells/mouse developed tumors within 14 to 21 days. CA 19-9 antigen was detected in the sera of all nude mice with SW1116 tumors, and antigen concentration correlated (r = 0.77) with tumor volume throughout the 9-week study. The half-life of this antigen in serum following tumor excision from nude mice was 6.5 +/- 1.5 (S.D.) hr. Carcinoembryonic antigen was also detected in serum from mice bearing SW1116 tumors by an immunoradiometric assay for carcinoembryonic antigen, but its concentration correlated (r = 0.86) with tumor volume for only the first 4 weeks of tumor growth. Significant levels of endogenous immunoglobulin G1 and immunoglobulin G3 antibodies to CA 19-9 antigen were found in the serum of nude mice with SW1116 tumors by radioimmunodiffusion, but no apparent relationship between antibody titer and tumor growth or CA 19-9 antigen level in serum was evident. This tumor model may be useful in devising radioimmunodetection and immunotherapeutic strategies for primary and metastatic human colon carcinomas.

Animals↗
PubMed1984

Clinical studies of prostatic cancer imaging with radiolabeled antibodies against prostatic acid phosphatase.

Conventional antibodies against prostatic acid phosphatase, labeled with iodine-131, have been administered to patients with prostatic carcinoma for the external scintigraphic imaging of tumors containing prostatic acid phosphatase (radioimmunodetection). The method has been found to be safe and reliable for imaging of primary tumors and non-bone metastases, even differentiating between lung tumors of prostatic and pulmonary origin.

Acid Phosphatase↗
PubMed1984

Future of nuclear medicine--impact of new radiopharmaceuticals and of alternative methods such as nuclear magnetic resonance.

Nuclear medicine (NM) is returning to its origin by studying more and more metabolic signals using new positron or single photon emitting radiopharmaceuticals. Much of the success that has been achieved by PET is now being transferred to SPECT-techniques. In contrast to static planar scans the changing tissue concentration of radiotracers can now be quantified. In this respect radioimmunodetection using monoclonal antibodies has a tremendous future. It is quite probable that 99mTc will continue to be the principle radionuclide. Especially radiopharmaceuticals for "hot spot"-imaging will be important in the near future, for example radioactively labelled blood cells. NM has a unique contribution to offer to nuclear magnetic resonance (NMR) because of its emphasis on physiologic as well as anatomic imaging parameters. NM can interact with the new revolutionizing technology of NMR in two ways: NM can help to understand NMR and NMR can help to identify regions of interest to be studied by NM. For example, we cannot see metabolic processes of the brain in NMR which are seen by biological radiotracers such as dopamin receptors in NM. However, there is no doubt, that NMR will also have a negative impact on NM. The potential value of NMR for in vivo biochemical analysis seems to be tremendous. The additional information gained by NMR about metabolic processes may well change our entire understanding of health and disease. The advantage that NM procedures can be performed on an outpatient basis will apply to NMR as well. NM and NMR will be complementary modalities in the future.

Heart Diseases↗
PubMed1983

Improved radioimaging and tumor localization with monoclonal F(ab')2.

Monoclonal anti-tumor antibodies have great promise for radioimmunodetection and localization of tumors. Fab and F(ab')2 fragments, which lack the Fc fragment of antibody (Ab), are cleared more rapidly from the circulation and may have less nonspecific tissue binding than intact Ab. In radioimaging studies using a murine monoclonal antibody to carcinoembryonic antigen in a human colon carcinoma xenografted into hamsters, F(ab')2 fragments were shown superior to Fab fragments and intact antibody for scintiscanning. In double-label experiments with anti-CEA antibody and control monoclonal IgG, F(ab')2 fragments were found to give better and more rapid specific tumor localization than intact antibody or Fab fragments. F(ab')2 fragments offer significant promise for tumor imaging and possibly therapy.

Animals↗
PubMed1983

Prostatic acid phosphatase: current concepts.

The development of antibodies to PAP opened a new horizon in the detection of acid phosphatase in serum and tissue. The advantages and limitations of this new methodology has been reviewed. A new utilization for PAP antibodies is radioactive labeling of these antibodies for radioimmunodetection of prostatic cancer metastases. If future studies in localizing metastatic sites are promising, then PAP antibodies labeled with chemotherapeutic agents or radioactive isotopes may have a role in therapy.

Acid Phosphatase↗
PubMed1983

Differential expression of tumor-associated antigens in human colon carcinomas xenografted into nude mice.

The tumor-associated antigen profile of a number of different human colon carcinomas xenografted into inbred Swiss nude mice was examined to determine whether the tumors could serve as useful models for antigen purification, radioimmunodetection, and immunotherapy. Extreme heterogeneity was observed both by radioimmunoassay and immunohistochemical procedures for the expression of carcinoembryonic antigen (CEA), colon-specific antigens (CSAp), and colonic mucin antigen (CMA) within the tumors. Four of 10 tumors (DLD-2, DLD-3, DLD-5, and HCT-10) were high producers of CEA (greater than 75 micrograms/g wet tissue wt). Two of these (DLD-2 and HCT-10) correlated with a high production of CSAp and CMA, whereas the other 2 produced low quantities of these antigens. Another tumor, HCT-14-OM1, produced large amounts of CMA yet produced moderate amounts of CEA and low quantities of CSAp. Immunohistochemical analyses of CEA gave a mostly diffuse cellular and cell surface staining for all of the tumors. Staining for CSAp was very focal, as in DLD-5 where only a few of the tumor cells were stained. Staining of CMA was limited; however, DLD-2, HCT-10, and HCT-14-OM1 showed intense cystoplasmic and intraluminal staining. A determination of the tumor antigen profile may be useful in characterization and classification of the tumor as well as enabling the selection of the proper antibody or antibodies for immunodetection and immunotherapy.

Animals↗
PubMed1983

Accumulation of radioactively labeled antithyroglobulin antibody by thyroid carcinoma.

The present experiments were undertaken to investigate (1) accumulation of radioactively labeled anti-thyroglobulin antibody by thyroid carcinomas and (2) the mechanism by which radioactively labeled antibody reaches to and stays in carcinoma cells. Anti-thyroglobulin antibody was purified by affinity chromatography using serum obtained from a patient with Hashimoto's disease. 125I-labeled anti-thyroglobulin antibody was injected into nude mice bearing transplanted human thyroid carcinomas. Scintigrams were taken 3 and 7 days after injection. Mice were killed thereafter and the radioactivity in each tissue and in serum was analyzed by gel filtration and affinity column chromatography of thyroglobulin, anti-thyroglobulin antibody and anti-human IgG antibody. In a total thyroidectomized patient with a metastatic thyroid carcinoma of the lymph node, 131I-labeled antibody was injected and scintigraphy and blood sampling performed for 7 days after injection. Scintigrams of the mice clearly showed the highest density over the transplanted carcinoma. Most radioactivity in the carcinoma was found to be in the thyroglobulin-antibody immune complex, while in other tissues, including serum samples, the radioactively was in free anti-thyroglobulin antibody. Scintigrams of the patient also showed a hot area over a metastatic carcinoma of the lymph node. It is concluded that (1) radioactively labeled anti-thyroglobulin antibody is accumulated by thyroid carcinoma in spite of the presence of thyroglobulin in blood and stays in cells as thyroglobulin-antibody immune complex, and (2) radioimmunodetection of thyroid carcinomas using labeled anti-thyroglobulin antibody is useful especially for patients with metastases which produces thyroglobulin and do not take up radioiodide.

Animals↗
PubMed1984

Radioimaging of the prostate and metastases of prostatic carcinoma with 99mTc-labelled prostatic acid phosphatase-specific antibodies and their Fab fragments.

A radioimmunodetection technique using 99mTc-labelled polyclonal antibodies raised in rabbits against human prostate-specific acid phosphatase was used to detect metastases of prostatic carcinoma. All the metastases observed by X-rays or bone scintigraphy in the four patients with M1-disease were revealed by the novel technique employed. In addition, in one of the patients studied, a distinct incorporation of radioactivity was also observed in the left inferior scapular region, which was not seen by conventional bone scanning, but was later confirmed by X-ray studies to be a metastatic process.

Acid Phosphatase↗
PubMed1980

Circulating immune complexes in cancer patients receiving goat radiolocalizing antibodies to carcinoembryonic antigen.

The circulating radioactivity and antibody immunoreactivity in patients with diverse cancers who had received 131I-labeled goat antibodies to carcinoembryonic antigen (CEA) were studied by Sephadex G-200 column chromatography and with solid-phase (SP) immunoadsorbents containing anti-goat immunoglobulin G(IgG), anti-human IgG, anti-CEA, or CEA. Upon gel filtration, more than 80% of the plasma radioactivity was distributed between native IgG and an excluded macromolecular radioactive fraction (Pool I). The native IgG and Pool I radioactive peaks were immunoreactive with the SP anti-goat IgG and SP CEA to the same extent as was the radioantibody prior to injection. The circulating CEA in patients with elevated titers only partially bound the injected radioantibody since less than 50% of the latter chromatographed as Pool I. Up to 50% of the Pool I radioantibody from this group of patients was bound to the SP anti-CEA, whereas it was minimally reactive with the SP anti-human IgG. The clearance of radioantibody was similar between groups having different amounts of Pool I radioantibody, and injection of CEA radioantibody was not accompanied by a decrease in circulating antigen. Patients with lower CEA titers had the majority of the plasma radioactivity chromatographing as Pool I radioantibody which showed elevated binding to the SP anti-human IgG but not the SP anti-CEA. Tumor localization by photoscanning was observed in seven of eight and nine of nine patients who had circulating CEA-radioantibody and anti-immunoglobulin-radioantibody complexes, respectively. Thus, these studies demonstrate that CEA, as well as human antibody reactive with goat IgG, can form immune complexes in patients given injections of CEA radiolocalizing antibody. However, these complexes do not appear to prevent tumor radioimmunodetection.

Animals↗
PubMed1982

The role of tumor markers in the management of colorectal cancer.

Among the tumor-associated antigens evaluated for the diagnosis and management of cancer, carcinoembryonic antigen (CEA) is the only established and clinically useful tumor marker for colorectal cancer and other CEA-producing tumors. Because of the exhaustive studies in the past decade, a consensus development conference was held at NIH in September 1980, to address the issue concerning the role of CEA as a marker in the management of cancer. This conference concluded that the use of regular and sequential assays of blood CEA is the best noninvasive technique for postoperative surveillance of patients to detect disseminated recurrence of colorectal cancer. The CEA level can serve as an indicator of successful or incomplete resection, and is useful in monitoring the effect of chemotherapy or radiotherapy. CEA can also provide a useful estimate of prognosis. CEA is neither sensitive nor specific enough to be used in routine screening for possible malignancy in an asymptomatic population. Nor can this test independently establish a diagnosis of cancer, but it can be used as an adjunct to clinical staging methods in known cancer patients. Radioimmunodetection and radioimmunotherapy with anti-CEA antibodies are currently being evaluated. Study of the pathophysiology and metabolism of CEA is needed. CEA remains the prototype tumor marker and is a valuable comparative tool, when investigating the clinical value of other newly developed tests for tumor markers.

Carcinoembryonic Antigen↗
PubMed1980

Tumor markers for radiommunodetection of cancer.

One of the potential uses of tumor-associated antigens or tumor markers, the localization of metastatic tumors using radioactive antibodies, has now been demonstrated and confirmed in clinical situations. The next stage of development in radioimmunodetection will be the improvement of techniques and methodologies. The selection of the optimal marker or markers to be used for localization is one area where improvement will be forthcoming. Guidelines for the choice of potential markers and methods for evaluation of potential markers before being clinically tested are presented in this article.

Antibodies, Neoplasm↗