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PubMed1989

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies].

Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with colorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with gamma-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer.

Aged↗
PubMed1987

Problems associated with radioimmunodetection and possibilities for future solutions.

It is the opinion of the authors that the molecule of the future for radioimmunodetection (and hopefully radioimmunotherapy and delivery of drugs) will have the following characteristics: It will be an altered fragment, rather than an intact molecule or fragment. It will be small, perhaps 60,000 molecular weight, yet remain in the vascular compartment for a comparatively long period of time, then be eliminated via the kidney. It will be of human origin or a murine molecule altered to mask its immunogenic properties. It will be 111In- or 99mTc-labeled or bifunctionally chelated to another metal ion. It will target a cell surface antigen, but one that does not circulate. It will be used in combination with derivatives of other MoAbs that target other antigens on the cell. It would be a hapten-type device that follows the administration of a "bifunctional MoAb." Whatever the final molecule, it will be administered to a patient who has been "prepped" with an antigen-enhancing substance or one that "unmasks" a gene and allows a repressed marker to be expressed by the tumor cell to which the MoAb was developed. It may be a MoAb that attaches to a white cell, which then chemotactically seeks the tumor that has been previously induced to produce a substance that the white cell recognizes.

Animals↗
PubMed1987

[Radioimmunodetection of human lung cancer xenografts by isotope labeling monoclonal antibody ALT-04 in nude mice].

Three nude mouse models bearing the human lung cancer were established from two fresh surgical specimens and one cell line. Tumor histological structure and cell morphology were similar before and after transplantation. The monoclonal antibody ALT-04 (McAb ALT-04) against human lung cancer was labeled by 125I, 131I and 201Tl. Radioimmunodetection study showed that all the three kinds of xenografts in nude mice were specifically located by McAb ALT-04. Imaging examination confirmed the ability of isotope labeling McAb ALT-04 to detect the presence of transplanted human lung cancer tissues without the aid of background subtraction manipulations. It is suggested that McAb ALT-04 have the possibility of locating in the tumor diagnosis and guiding in the treatment.

Animals↗
PubMed1986

A human colon cancer metastasis model for radioimmunodetection.

One important issue in radioimmunodetection is how well the current methods can locate and disclose small metastatic foci in visceral sites. We have developed a human colonic tumor metastasis model by surgically implanting GW-39 tumor cells in the liver of unconditioned hamsters. Tumors were produced in 71 of 73 animals and were macroscopically apparent within 1 wk. In addition, multiple nodular lung metastases of GW-39 were found in about 80% of the animals given implants of tumor in the liver, but implantation of tumor in the spleen failed to show lung metastases even after 4 wk. Hamsters bearing GW-39 liver and cheek pouch grafts or normal hamsters were given injections of a mixture of 131I-labeled anti-carcinoembryonic antigen antibody and 125I-labeled irrelevant immunoglobulin G. After 7 days, tumor was localized by external scintigraphy without subtraction techniques in both the liver and cheek pouch, but even in animals with extensive lung metastases we failed to unequivocally detect tumor in the lungs by external imaging or by comparing tissue counting data from uninvolved and tumor-bearing lungs. However, whole-body autoradiography confirmed specific localization of anti-carcinoembryonic antigen antibody in the tumors at all sites indicating that tissue counting and external imaging were not sensitive enough to reveal micrometastatic tumors. Thus, the current methods used for this model appear to be useful for further investigation of the radioimaging of tumors growing in visceral organs.

Animals↗
PubMed1986

Radioimmunodetection of malignant melanoma with the 225.28S monoclonal antibody to HMW-MAA.

A review of the studies on the use of the antigen-antibody system HMW-MAA 225.28S in melanoma radioimmunodetection is reported. The results obtained in a pilot study (42 patients with 74 lesions), a multicenter trial (254 patients with 553 lesions) and a prospective study still outstanding (29 patients with 38 lesions) allow to consider this system as suitable for clinical application. F(ab')2 labelled with 99mTc gave the best results in terms of positivity. Moreover this radioisotope allows the best dosimetric conditions. The gamma energy emitted by this radionuclide is particularly convenient for conventional scintillation cameras and ECT. Very good results in terms of sensitivity (70%-85%) and especially specificity (about 100%) were achieved. Possible clinical applications of the method are discussed.

Antibodies, Monoclonal↗
PubMed1987

Radioimmunodetection of cancer with the use of indium-111-labeled monoclonal antibodies.

We have infused 13 111In-labeled murine IgG monoclonal antibodies (MAb) into 73 patients who had been diagnosed as having 7 types of cancers, and 3 111In-labeled human MAb into 8 patients with breast cancer. To each patient, 1.5-5 mCi attached to a maximum of 1 mg MAb had been given in a total MAb dose of 0.5-500 mg. The most encouraging overall results have been obtained with anti-human T-cell MAb T101 (33 of 33 tumor sites imaged in 5 patients), antimelanoma MAb P96.5 (47 of 88 sites imaged in 21 patients), anti-prostate MAb PSA399 (14 of 21 sites imaged in 4 patients), and anti-colon MAb ZCE025 (16 of 26 sites imaged in 12 patients). Poor imaging results were related to lower doses, reactivity with circulating cells, and limited antigen expression in various tumor sites. The problems involved in radioimmunodetection included low extraction of MAb from the serum by the tumor that resulted in poor tumor uptake of the radiopharmaceutical, and high background activity in the liver, heart, spleen, and gastrointestinal tract that made imaging difficult in those areas. Heterogeneous antigen production leaves some tumor deposits without targets, and the immunogenicity of the MAb limits use of these agents repetitively in humans. Nevertheless, these early results are encouraging for their potential diagnostic and therapeutic applications.

Antibodies, Monoclonal↗
PubMed1984

Analysis of radioimmunodetection of tumors by the subtraction technique.

The subtraction method for radioimmunodetection (RID) of cancer is showing potential as a diagnostic tool. An objective assessment of this technique is needed in order to determine its clinical usefulness. A numerical analysis of the RID scintigrams was developed and applied to 21 RID studies on 20 patients for whom a final diagnosis had been established. The subtraction technique was shown to give rise to artifactual positive regions, which could be avoided by experienced clinicians. When artifact-producing regions were excluded, 97 regions were examined (80 nontumor, 17 tumor-containing). The "background" scintigrams were shown to be good models for nontumor regions of the antibody scintigrams, and tumor and nontumor regions were shown to form statistically distinct groups.

Antibodies↗
PubMed1984

Lack of radioimmunodetection and complications associated with monoclonal anticarcinoembryonic antigen antibody cross-reactivity with an antigen on circulating cells.

Characterization of several high-affinity murine monoclonal anticarcinoembryonic antigen (CEA) antibodies suggested good specificity except for cross-reactivity with an antigen on granulocytes and erythrocytes which was different from the previously described normal cross-reacting antigen of granulocytes. In vivo studies in athymic mice using an indium conjugate of an anti-CEA monoclonal antibody (MoAb) revealed excellent specific uptake in colorectal carcinoma xenografts. Studies were conducted in humans to determine the limitations produced by the cross-reactivity with granulocytes and erythrocytes. Patients with metastatic colorectal cancer received 3 to 6 mg of anti-CEA MoAb over 10 min or 2 hr. In five of six trials, the MoAb infusion was associated with a 40 to 90% decrease in circulating granulocytes and systemic toxicity including fever, rigors, and emesis. One patient had no change in cell count and had no toxicity. Radionuclide scans with 111In-anti-CEA MoAb showed marked uptake in the spleen when cells were eliminated, and in the liver, especially when pretreatment CEA levels were high. Metastatic tumor sites failed to concentrate the isotope. This study emphasizes the potential limitations for radioimmunodetection and/or radioimmunotherapy imposed by reactivity with circulating cells, and suggests that certain toxic reactions associated with MoAb infusions are related to destruction of circulating cells rather than allergic reactions to mouse protein. It also emphasizes how variables such as dose and binding affinity of antibody, radioisotope used, and assessment at different observation points can obscure lack of antibody specificity.

Animals↗
PubMed1980

Immunological considerations in the use of goat antibodies to carcinoembryonic antigen for the radioimmunodetection of cancer.

Preparation of radioantibodies from carcinoembryonic antigen (CEA) antisera raised in goats by conventional procedures necessitates extensive absorption procedures to remove antibody activity against CEA-related substances. Further purification by affinity chromatography increases the antibody content of the radiolabeled preparation and enhances antibody uptake by a xenogeneic tumor. In patients given injections of CEA radioantibody, immune complexes form with CEA or a human antibody reactive with goat gamma-globulin, but these complexes do not appear to prevent tumor radioimmunodetection. Monoclonal antitumor antibodies from appropriate animal species would be a more suitable source, eliminating many of the problems encountered with conventional antisera.

Animals↗
PubMed1998

Radioimmunodetection of human myeloma xenografts with a monoclonal antibody directed against a plasma cell specific antigen, HM1.24.

BACKGROUND: To develop a new immunologic approach to multiple myeloma, the authors generated a monoclonal antibody against a human plasma cell specific antigen, HM1.24. Their previous study showed the antitumor effect of this antibody in severe combined immunodeficiency (SCID) mice bearing human myeloma xenografts. In the current study, the efficacy of anti-HM1.24 immunoglobulin (Ig) G and its F(ab')2 fragment were evaluated for radioimmunologic detection of the myeloma xenografts. METHODS: SCID mice bearing subcutaneous RPMI 8226 tumors were injected with 125I-labeled antibodies, and radioactivity in the tumor and normal tissues was measured. Radioimmunoscintigraphy and autoradiography were performed to investigate the distribution of the antibodies. RESULTS: In comparative biodistribution studies, the maximum tumor localization index of anti-HMl.24 F(ab')2 fragment was significantly higher than that of anti-HM1.24 IgG. Anti-HM1.24 F(ab')2 consistently had higher tumor-to-tissue ratio than anti-HM1.24 IgG and gave distinct tumor images by radioimmunoscintigraphy. Autoradiographic study showed that anti-HM1.24 F(ab')2 penetrated the tumor mass more uniformly than whole IgG antibody. CONCLUSIONS: These results indicate that anti-HM1.24 antibody has the potential to provide a new approach to the immunodetection and immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Animals↗
PubMed1998

Intraoperative radioimmunodetection.

The radioimmunoguided surgery (RIGS) system employs a monoclonal antibody (CC49), a radionuclide (Iodine-125), and a hand-held gamma-detecting probe (the Neoprobe model 1000). The prototype cancer studied has been colorectal cancer. The antibody identifies a type of mucin, the by-product of the adenocarcinoma cancer cell. The RIGS system localizes up to 90% of colorectal cancers and finds additional RIGS-positive tissues in >50% of the patients. More than 90% of the RIGS-positive visceral tumors are identified by routine hematoxylin-and-eosin (H&E) light microscopy, but the RIGS-positive lymph nodes are H&E occult tissues in >70% of the cases. Enhanced, more time-consuming methods have been developed to confirm hidden cancer cells in these lymph node tissues. Survival data confirm the importance of RIGS-positive tissues. RIGS-positive tissues remaining at the completion of the surgical procedure portend a much poorer outcome than if the patient is deemed RIGS-negative at the completion of the surgical procedure (i.e., all RIGS-positive tissue was removed at surgery).

Antibodies, Monoclonal↗
PubMed1992

Radioimmunodetection and autoradiographic localization of monoclonal antibody against human hepatocellular carcinoma in xenografts.

The monoclonal antibody against human hepatocellular carcinoma, HAb23, was conjugated with radioiodine and injected into nude mice with human hepatoma xenografts. After 4 to 5 days, the nude mice were scanned by emission computerized topography. The results showed that the xenografts were distinguished clearly. The tumor-liver and tumor-blood ratios were 1.94 to 3.66 and 0.56 to 1.65, respectively. Autoradiography showed that the HAb23 was localized mainly on the surface membrane and tubulovesicular systems of the tumor cells.

Animals↗
PubMed1993

Real-time kinetic analysis applied to the production of bispecific monoclonal antibodies for radioimmunodetection of cancer.

An automated biosensor system designed for measuring molecular interactions in real-time and without labelling of the reactants has been used to evaluate the association/dissociation rate and affinity constants of bivalent monoclonal antibodies and a monovalent bispecific monoclonal antibody. Observed differences in affinity between parental and bispecific antibody produced were related to the association rate constants, since the dissociation rate constants were in the same range. Values were also closely related to radioimmunochemical data. These results indicate that the biosensor system, besides presenting several advantages for characterizing antigen-antibody interaction, is valuable for selecting monoclonal antibodies with properties which might be useful in the development of bispecific monoclonal antibodies.

Antibodies, Bispecific↗
PubMed1993

Radioimmunodetection of lung cancer with IMACIS-1, I-131 labeled monoclonal antibodies to CEA and CA19-9. Comparison of accumulations in irradiated and non-irradiated site.

IMACIS-1 is a radiopharmaceutical containing a mixture of Iodine-131 labeled monoclonal antibodies to CEA and CA19-9. IMACIS-1 immunoscintigraphy was evaluated for tumor detection in 7 primary lung cancer and 2 metastatic lung cancer patients who received radiotherapy. No adverse side effects due to IMACIS-1 were observed in this study. Positive detection was achieved in 5 of 9 patients (55.6%). It was less, but nearly the same as the detection rate obtained with Gallium-67 citrate (67Ga-citrate) in these patients. There was no clear correlation between IMACIS-1 accumulation and the CEA or CA19-9 serum levels. The IMACIS-1 positive detection rate decreased in many of the irradiated lesions. We considered that the decreased number of tumor cells and changes in blood perfusion are some of the factors controlling accumulation in tumors.

Adenocarcinoma↗
PubMed1994

Radioimmunodetection of cancer of gastrointestinal tract and liver metastasis with I-131 anti-CEA and I-131 anti-CA19-9 monoclonal antibody cocktail (IMACIS-1).

We evaluated the intravenous infusion of a cocktail of I-131 anti-CEA and anti-CA19-9 monoclonal antibody F(ab')2 (IMACIS-1) in patients with gastrointestinal neoplasm and liver metastases in order to assess its efficacy in detecting the presence of cancer. Seven patients with primary or recurrent gastrointestinal cancer in whom liver metastases were also detected were studied. Accumulation of radioactivity in the primary tumor was seen in only one patient. Visualization of the liver metastases was achieved in all patients. Thus detection of liver metastasis was better than in primary or recurrent tumors. While tumor visualization was most often seen in the 3 day image, optimal visualization of the tumor was seen at 5-7 days. There was no correlation between the serum concentration of CEA or CA19-9 and the visualization of tumors. Serum kinetics of I-131 IMACIS-1 showed biexponential components with a 1st phase T1/2 of 5.0 hours and 2nd phase T1/2 of 34.7 hours. The mean whole body (I-131) half-life determined from the whole-body scans was 1.95 days. The mean urinary excretion of I-131 in 7 days was 85%. This value agreed closely with total radioactivity retention detected by scanning. This series of studies demonstrated the potential utility of a cocktail of antibodies consisting of an anti-CEA and an anti-CA19-9 monoclonal F(ab')2.

Aged↗
PubMed2000

Radioimmunodetection of residual, recurrent or metastatic germ cell tumors using technetium-99 anti-(alpha-fetoprotein) Fab' fragment.

PURPOSE: The majority of patients with germ cell tumors are cured by multimodality therapy that consists of cisplatin-based chemotherapy and/or surgical resection. Serum tumor markers and conventional radiographs are utilized to stratify patients into treatment categories. Efforts to individualize chemotherapy or minimize surgical interventions without compromising outcome are important. Immunomedics (Morris Plains, New Jersey) developed an anti-(alpha-fetoprotein) (anti-AFP) monoclonal antibody IMMU-30 labeled with 15-20 mCi technetium-99, and the purpose of this study is to determine the sensitivity and specificity of radioimmunoscintigraphy using 99mTc anti-AFP antibody for the diagnosis of active germ cell tumors. METHODS: A group of patients with germ cell tumors were enrolled in a non-prospective fashion and 48 AFP scans using 99Tc anti-AFP Fab' fragment were obtained. At the time of the AFP scan, serum AFP was elevated in 40 measurements with a median level of 21 ng/ml (1.6-66, 210.0 ng/ml). AFP scans were obtained at the initial staging, during treatment, at relapse or at long-term follow-up and compared with conventional radiographs done within 4 weeks of the AFP scans. RESULTS: An overall diagnostic sensitivity of 89% and specificity of 58% were obtained. CONCLUSIONS: AFP scanning appears useful and to be sufficiently sensitive to justify prospective studies comparing the procedure with conventional imaging.

Adolescent↗
PubMed1992

Radioimmunodetection of human colon cancer using 99mTc-MDP-MoAb-A7 in mice.

Radioimmunoscintigraphy (RIS) using 99mTc-labeled A7, a monoclonal antibody (MoAb) against a human colorectal cancer, was performed in nude mice bearing a human colon cancer, HCT-15. MoAb-A7 was labeled with 99mTc in the presence of methylene diphosphate (MDP). At 24 h post-injection of 99mTc-MDP-A7, colon cancer was clearly visualized, and the tumor-to-tissue ratio of 99mTc-MDP-A7 was higher than the ratio of 111In-DTPA-A7 which was described previously. These results suggest the possibility of the clinical application of 99mTc-MDP-A7 for RIS of a human colon cancer.

Animals↗