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PubMed1989

The effect of circulating antigen on radioimmunodetection and monoclonal antibody localisation: studies in a normal rat model.

The effect of circulating antigen (human kappa light chains (LC] on radioimmunoscintigraphy was examined in a normal rat model. Rats were implanted subcutaneously with kappa (test) and lambda (control) LC coupled to sepharose beads (500 micrograms LC/ml swollen gel). When 131I-labelled monoclonal antibody, K-1-21 was injected, clear images of specific antibody localisation to the kappa implant were seen 6 days later. The kappa implant: blood ratio (K:B) was 7.69 +/- 0.45, which represented an implant uptake of 2.52 +/- 0.20 percent injected dose per gram (%ID/g). When 131I-K-1-21 was preincubated with 125I-kappa LC at ratios of up to 1:10 antibody: antigen, (w/w) before injection; or if antigen was given daily by bolus injection or continuously infused via an osmotic pump, very clear specific images of antibody localisation to the kappa implant were still obtained. There was, however, a decline in the absolute uptake of label by the kappa implant. The greatest change was observed following continuous antigen infusion, when kappa implant uptake fell to 1.26 +/- 0.1 %ID/g. Nevertheless, the K:B ratio was still maintained at 6.8 +/- 0.2, due to increased clearance of antibody from the blood. Thus, in this case, where antigen and antibody might be expected to form small, soluble immune complexes, there was no major deleterious effect on radioimmunoscintigraphy.

Animals↗
PubMed1985

Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector.

A hand-held gamma detection probe was used intraoperatively to localize primary and recurrent colorectal tumors in 28 patients 48 to 72 hours after they received an intravenous injection of 2.2 mCi of iodine-131 labeled anticarcinoembryonic antigen polyclonal baboon antibody. Preoperative evaluation included determination of serum carcinoembryonic antigen, barium enema, colonoscopy, chest film, computerized axial tomography, liver, spleen, and bone scans, and endoscopy when indicated. Preoperative whole-body imaging correctly localized primary tumors in only 33 percent of the patients, whereas it correctly demonstrated tumor in 64 percent of those with recurrent disease. Intraoperative tumor-to-background ratios derived from the detector probe were elevated in all patients, averaging 3.97:1 in primary lesions and 4.18:1 in recurrent tumors. Postoperatively, carcinoembryonic antigen was localized in tissues with the avidin-biotin peroxidase staining technique to confirm intraoperative readings. Variations in stain uptake in a patient could be correlated with variations in radiation detector readings in the same patient. Results support our previous work in nude mice, demonstrating the improved sensitivity and specificity of the hand-held gamma detection device over whole-body imaging for intraoperative localization of immunoradiolabeled tumors.

Animals↗
PubMed1986

Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')2 fragments.

Experimental procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice as compared to experimentally immunosuppressed mice due to the higher viability of the tumors in nude mice. MAb localization in tumor tissue was greatly enhanced when F(ab')2 fragments rather than intact antibody molecules were used. Although tumors could be visualized with either 131I-, 123I- or 111In-labeled MAb fragments without using background subtraction, tumor-to-background ratios of radioactivity were highest for 131I-labeled fragments. 131I-labeled F(ab')2 fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by gamma-scintigraphy. On the other hand, some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')2 fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone. Thus, Scatchard analysis of MAb binding to tumor cells may be an effective means to screen for MAb with tumor radiolocalization potential.

Animals↗
PubMed1986

Radioimmunodetection of human melanoma tumor xenografts with human monoclonal antibodies.

We established a human IgM monoclonal antibody that defines a tumor-associated membrane antigen expressed on human melanoma cells. The antigen has been identified as the ganglioside GD2. In this paper, we describe the potential usefulness of the human monoclonal antibody for radioimaging. Nude mice bearing tumors derived from a human melanoma cell line were used as a model. Antibody activity was degradated significantly after labeling with 131I by the use of a modified chloramine-T method. After testing various concentrations, labeled antibody of a specific activity of 2.8 microCi/micrograms produced the best results. Balb/c nude mice bearing a GD2-positive M14 melanoma cell line were injected with 10-30 micrograms of labeled antibody, and its radiolocalization in different organs and in the whole body were evaluated. The best tumor image was obtained on Day 6. The labeled antibody uptake ratio between tumor and muscle was 9.2:1; the ratio between tumor and liver was 1.4:1. These studies represent the first report of experimental tumor imaging with human monoclonal antibody. Human monoclonals with probably prove to be superior reagents for tumor imaging in melanoma patients if the problem of antibody radiolysis is resolved.

Animals↗
PubMed1982

Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody.

In 10 out of 11 patients with colorectal cancer radiolabelled antitumour monoclonal antibody (791T/36) was localised to the tumour. The mean tumour to non-tumour uptake ratio of antibody demonstrated by imaging with a gamma camera was 4.4/1 after subtraction of background radioactivity. The antibody did not localise in one patient who had received radiotherapy to his tumour two weeks previously. In 5 patients with primary neoplasms localisation of the antibody was confirmed by further imaging of the resected specimens and in-vitro radioactivity counting of the tumour and comparison with the activity in adjacent normal colon.

Adult↗
PubMed1988

Radioimmunodetection of cancer with monoclonal antibodies: current status, problems, and future directions.

Early studies of immunoscintography with affinity-purified 131I-labeled polyclonal antibodies reactive against oncofetal antigens such as carcinoembryonic antigen (CEA) were moderately successful in detecting metastatic colorectal carcinoma. However, because of low tumor to background ratios of isotope, background subtraction techniques using 99Tc-labeled albumin were required to visualize small lesions. Antisera were often of low titer and lacked specificity. These problems could be overcome for the most part following the development of highly specific monoclonal antibodies (MoAb) against a variety of tumor-associated antigens. A number of clinical trials using 131I- or 111In-labeled MoAb to image tumors have demonstrated successful localization without the use of subtraction techniques. Variables limiting the usefulness of murine MoAb for diagnosis have included increased localization in liver and spleen, tumor vascularity and heterogeneity of antigen expression, and development of human antimurine globulins. Methods to overcome some of these problems are discussed. Radiolabeled MoAb appear useful as an adjunct to conventional diagnostic techniques both as a means to predict which antibodies might be useful for treatment and, in select patients, as a basis for treatment decisions.

Animals↗
PubMed1984

Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.

The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr after injection of the second antibody and to enhance tumor/nontumor ratios within 24 hr. Unlike liposomally entrapped second antibody, the primary anti-CEA antibody did not show increased accretion of radioactivity in the liver, spleen, or other major organs. These results suggest that administration of a second antibody alone may improve tumor imaging with a radiolabeled antitumor antibody.

Animals↗
PubMed1991

A transition metal complex (Venus flytrap cluster) for radioimmunodetection and radioimmunotherapy.

A novel transition metal complex, Venus flytrap cluster (VFC), is described for the preparation of radio-labeled antibodies. VFC contained 57Co, which was held tightly between the faces of two covalently bridged carborane ligands by cluster bonding of the metal with appropriate ligand orbitals. Anti-carcinoembryonic antigen monoclonal antibody T84.66 was conjugated to 57Co-VFC with full retention of immunological activity. Biodistribution studies in nude mice bearing carcinoembryonic antigen-producing tumors showed excellent tumor localization of 57Co-VFC-T84.66. The accumulation of radionuclide in normal liver was low and independent of dose, which may reflect the stability of the radionuclide complex. These results presage the use of VFC systems for binding transition metals that are clinically useful for radioimmunodiagnosis and radioimmunotherapy.

Animals↗
PubMed1990

Effect of cross-reactivity of alpha-fetoprotein monoclonal antibody on quantitation of serum AFP and radioimmunodetection of hepatocellular carcinoma.

Murine hybridomas were generated by immunizing mice with purified alpha-fetoprotein (AFP) to determine the cross-reactivity of AFP antibodies with human serum albumin (HSA). Eighteen out of 23 hybridoma products were cross-reactive with HSA. All 23 monoclonal antibodies (MAbs) could be subgrouped into 3 groups by their binding affinity to AFP and HSA, and one MAb from each group, IIB3, IIIB1 and IIIC6, were chosen for this study. The affinity to AFP was highest for IIB3 followed by IIIC6 and IIIB1, and that to HSA was in the order IIIB1 greater than IIB3. Immunohistochemical staining revealed no cross-reactions of these antibodies with HSA at the tissue level. IIB3 was the most efficient in the quantitative assays, indicating high affinity and specificity (non-cross-reactivity) of the antibodies, both of which are prerequisites for in vitro assays. Scans with good tumor localization were obtained from mice which received 131I-labeled IIB3 or IIIC6 after xenografting of the human hepatocellular carcinoma. The images obtained with IIB3 were inhibited in the presence of either AFP or HSA in the circulation. These findings indicated that the use of cross-reactive and/or high-affinity antibodies against AFP provides an inhibitory factor for tumor localization. MAb IIIC6, because of its high specificity and moderate affinity to AFP, seems to be the best candidate for immunoscintigraphy of the tumors in future studies.

Animals↗
PubMed1986

Monoclonal antibody imaging of human melanoma. Radioimmunodetection by subcutaneous or systemic injection.

Fab fragments of monoclonal antibodies (MoAb) to melanoma, radiolabeled with 131I, were evaluated as diagnostic reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight antigen (HMW), or 96.5, which identifies a transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled antibodies demonstrated excellent nodal delineation without specific identification of tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed tumor in nodes. Of patients injected with Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma antibodies was observed in some patients in lymph nodes not containing tumor and was possibly related to antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection. Melanoma metastases can be identified with IV or SQ injection or radiolabeled antibodies. These reagents may be useful in the diagnosis or therapy of human melanoma. Further evaluation will be required before they could be considered clinically useful.

Adult↗
PubMed1997

Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer.

OBJECTIVE: The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical evaluation of patients with recurrent or metastatic colorectal carcinoma. SUMMARY BACKGROUND DATA: Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities. METHODS: In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings. RESULTS: Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%. CONCLUSIONS: The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.

Adult↗
PubMed1990

Radioimmunodetection of chemodectoma by In-111 labeled anti-CEA antibody. Case report and review of the literature.

The carotid body paraganglioma is a rare tumor that arises from the autonomic nervous chemoreceptor. It can be diagnosed by contrast angiography. A patient in whom a carotid body chemodectoma was imaged with In-111 labeled monoclonal anticarcinoembryonic antigen (anti-CEA) antibodies is described. There was marked accumulation of the antibody into the tumor but little blood pool activity at 25 hours. The removed tumor, which was examined immunohistochemically, was positive for vimentin, GFAP, NF 68, SYP, and S-100; and negative for CEA, desmin, and cytokeratin. The tumor was a paraganglioma that accumulated antibody with nonspecific mechanism of uptake.

Aged↗
PubMedDate not supplied

Monoclonal antibody radioimmunodetection of human-derived colon cancer.

This study was designed to determine whether monoclonal antibody directed against carcinoembryonic antigen could successfully be used in the scintigraphic localization of a human-derived colon carcinoma in a hamster model. An immunoglobulin G (IgG)-1 kappa monoclonal antibody, prepared in this laboratory, against carcinoembryonic antigen (CEA) was radiolabeled with iodine-131 (131I). Four Syrian hamsters bearing GW-39 human colon cancers received intracardiac injections of 50 mu Ci of 131I (14 micrograms of antibody). Gamma camera images were obtained at 24-hour intervals. Animals were sacrificed at 11 days, and the tumors and entire animals were counted. A double-label antibody experiment was conducted with 131I anti-CEA and nonspecific MOPC 21 IgG iodine-125 (125I) to assess localization specificity. The scintiphotos clearly showed the tumor at 24 hours, but there was significant background (blood-pool activity). Later images at six and 11 days showed a gradual decrease in background activity and more clear definition of the tumor. Animals sacrificed at 11 days showed 48-80% of residual whole body radioactivity to be present in the tumor. However, these tumors were large at sacrifice, weighing 8.9 to 12.4 g. Specific localization was confirmed by the double-label experiments where specific localization was twice nonspecific accretion of IgG in the tumor. This study has shown that a specific monoclonal antibody can successfully be used to scintigraphically localize a colon tumor of human origin. Although clearance of background activity is a gradual process, eventually most radioactivity left in the animal is localized in the tumor. This study illustrates that the potential radiolabeled monoclonal antibodies hold as immunodiagnostic agents.

Animals↗
PubMedDate not supplied

Radioimmunodetection of a transplantable human bladder carcinoma in a nude mouse.

The results of an in vitro mixed hemadsorption (MHA) assay predicted the success of in vivo tumor localization using a radioiodinated, monoclonal, IgG1 antibody (A2) with reactivity to the human bladder carcinoma cell line RT4. In vitro, murine monoclonal antibodies A2 and G6, demonstrated reactivity to RT4 with titers of 1/1024 and 1/4 by MHA assay, respectively. In vivo results obtained with RT4 xenografts in athymic nude, Balb/c, mice indicated tumor uptakes of 1.10% dose/gram with A2 and 0.29% dose/gram with G6 at seven days after radiotracer injection. Successful scintigraphic imaging of tumor xenografts was achieved with A2 but not with G6 or radioiodinated mouse serum albumin.

Animals↗
PubMed1987

An evaluation of anti-insulin radioimmunodetection in patients with suspected insulinoma.

Nine patients with suspected insulinoma were scanned with iodine-131 labelled anti-insulin. The clinical diagnosis was subsequently confirmed at laparotomy in eight patients, two of whom had liver metastases. The primary insulinoma was accurately localized by anti-insulin scanning in four patients and these tumours ranged from 1 to 3 cm in diameter. Both computerized axial tomography (CT) scanning and pancreatic angiography had given false negative results in one of these patients. Hepatic metastases were correctly identified in one of two patients. No hepatic false positive reports occurred. Positive scan areas were graded as definite, probable or possible. All four of the pancreatic positive results graded as definite or probable positive were correct. Three false positive results occurred in the region of the pancreatic body, all had been graded as possible. Anti-insulin scanning failed to detect four subsequently proven insulinomata (3 mm-2 cm in diameter). Pelvic uptake of anti-insulin occurred in a patient who was found to have a para-ovarian tumour. An homogenate of this tumour also reacted with anti-insulin in a radioimmunoassay. A true negative pancreatic scan was obtained in this patient. We conclude that this technique is insufficiently accurate for routine clinical use.

Adenoma, Islet Cell↗
PubMed1980

Clinical radioimmunodetection of cancer with radioactive antibodies to human chorionic gonadotropin.

Injection of iodine-131-labeled goat immunoglobulin G antibody to human chorionic gonadotropin (hCG) into patients with hCG-secreting trophoblastic and germinal tumors permitted tumor detection and location by external gamma-ray scintigraphy. Excision of one of the metastatic tumors located by this method indicated a tumor/nontumor ration of 39.29. The method appears to offer a new clinical tool for precisely locating hCG-producing tumors in the body, even when tumor identification by other clinical methods has failed.

Antibodies↗