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PubMed1993

Radioimmunodetection of Hodgkin's disease and non-Hodgkin's lymphomas with monoclonal antibody to eosinophil peroxidase.

The purpose of this study was to determine if a radiolabeled murine monoclonal antibody (EOS) directed against eosinophil peroxidase would localize specifically to tumor sites in patients with lymphomas infiltrated by eosinophils. Ten patients with Hodgkin's disease and eosinophilia, three patients with non-Hodgkin's lymphomas and eosinophilia and five control patients received an intravenous injection of 3-10 mg of EOS antibody radiolabeled with 74-155 MBq (2.0-4.2 mCi) of 111In. At intervals of 24, 48 and 72 hr after injection, gamma camera images were obtained along with blood and urine specimens and the imaging results were correlated with the results of other staging modalities. As early as 24 hr after antibody injection, there was clear visualization of identifiable sites of lymphoma with eosinophilia greater than 1 cm in size, including the spleen, bone marrow and lymph nodes. Although EOS also localized nonspecifically to the liver and, in some patients, to the nasopharynx, there was no appreciable uptake in normal bone marrow, spleen, uninvolved lymph nodes, lymphomas without eosinophilia or various other pathologic conditions without eosinophilia. Except for transient pain at tumor sites in three patients, no adverse reactions were noted. We conclude that a radiolabeled monoclonal antibody directed against eosinophil peroxidase localizes to lymphoma sites infiltrated by eosinophils.

Adult↗
PubMed1993

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA102: experience of 20 cases].

The monoclonal antibody CEA 102 against carcinoembryonic antigen was produced by immunization with purified CEA, and used as a radiotracer for the imaging of colorectal cancer. CEA102 was labeled with 131I by the chloramine-T or the Iodogen method, and administered i.v. to 20 patients with liver metastases, local recurrences, and/or primary tumors. Planar scintigraphy was performed during 5 or 6 postinfusion days. Hypersensitivity reactions such as fever and chill occurred in 4 patients, but no side effects were noted after endotoxin was excluded. Overall sensitivity was 71.4% (primary tumor 4/4, liver metastasis 5/6, lymph node metastasis 1/1, local recurrence 5/10), and no false positive was observed. In the cases of local recurrences, this method was useful to distinguish postoperative fibrosis from local recurrence. These results revealed that radiolabeled CEA102 has a great potential in qualitative diagnosis of colorectal cancer.

Adult↗
PubMed1998

Radioimmunodetection of medullary thyroid carcinoma using indium-111 bivalent hapten and anti-CEA x anti-DTPA-indium bispecific antibody.

UNLABELLED: Pretargeting labeled bivalent hapten with bispecific antibodies has proven feasible in the clinic, and our earlier results have suggested the technique may be very sensitive for detecting small recurrences and metastases. Medullary thyroid carcinoma (MTC) is an example where this technique may be the most useful since local recurrences and isolated metastases are removed surgically when detected, and thyrocalcitonin provides a specific and sensitive tumor marker. In our current study, we evaluated pretargeted immunoscintigraphy in a larger number of MTC patients. METHODS: Anti-carcinoembryonic antigen (CEA) x anti-diethylenetriaminepentaacetic acid (DTPA) indium bispecific antibody and 111In-labeled bivalent DTPA hapten were administered sequentially (4-5 days apart) to 44 patients with elevated circulating calcitonin after resection of primary MTC. Immunoscintigraphy was performed 2, 5 and 24 hr after hapten injection and, when necessary, at longer time intervals. When available, a handheld gamma probe was used during surgery. RESULTS: Fifteen patients had known tumor sites before immunoscintigraphy. Tumors were imaged in 12 (80%) of these patients, including 3 with liver metastases. Five unknown tumor sites were detected. For the 29 patients with occult disease, immunoscintigraphy detected high-activity uptake sites in 21 patients (72%), including 5 in the liver. Twelve were confirmed by surgery, 1 by guided morphologic imaging and 1 by venous catheterization. There were 2 false-positive patients. The other 5 patients have not yet been confirmed. All detected liver metastases were high-activity uptake areas. Radioimmunoguided surgery was used in 14 patients. It was considered helpful by the surgeon in 12 patients, including 4 patients where it determined the resection of small, not palpable nor visible, tumor-involved lymph nodes. Surgical resection resulted in a significant decrease (8 patients) or normalization (1 patient) of circulating calcitonin and CEA. CONCLUSION: This technique affords high sensitivity and specificity for detecting small tumor lesions including liver metastases. Its use for immunoscintigraphy and guided surgery should improve the therapeutic management of recurrent MTC.

Adult↗
PubMed1989

The use of a monoclonal antibody against alpha-fetoprotein for the radioimmunodetection of hepatocellular carcinoma.

The purpose of this study was to investigate the use of a radiolabeled mouse monoclonal antibody (and its F(ab')2 fragment) against alpha-fetoprotein in the scintigraphic diagnosis of hepatocellular carcinoma. Twenty-six southern African Blacks and one Caucasian with hepatocellular carcinoma and four patients with other malignant tumors of the liver were studied. Although six hepatocellular carcinomas appeared to selectively concentrate alpha-fetoprotein antibody, one of these tumors was not producing alpha-fetoprotein. Moreover, in another 18 patients with alpha-fetoprotein-producing hepatocellular carcinomas, uptake of alpha-fetoprotein antibody was at best only equal to that in nontumorous hepatic tissue, and three hepatocellular carcinomas that were not producing alpha-fetoprotein concentrated the antibody to the same extent as did the alpha-fetoprotein-producing tumors and hepatic tissue. All four tumors other than hepatocellular carcinoma concentrated alpha-fetoprotein antibody as well as did hepatic tissue. These findings suggest that the penetration of hepatocellular carcinomas by alpha-fetoprotein antibody is a passive and nonselective process. This conclusion is supported by an in vitro study in which a non-alpha-fetoprotein-producing hepatic metastasis took up as much radiolabeled alpha-fetoprotein antibody as did three of four alpha-fetoprotein-producing hepatocellular carcinomas. A likely explanation for the failure of alpha-fetoprotein monoclonal antibody to be selectively concentrated by hepatocellular carcinomas is that alpha-fetoprotein is an export protein and is not expressed on the cell membranes of malignant hepatocytes.

Adult↗
PubMed1987

Multiple epitope recognition: an approach to improved radioimmunodetection of tumor-associated antigens.

Three MAbs endowed with comparable affinity for 3 distinct epitopes of a HMW-MAA have been employed to study whether the use of combinations of MAbs might improve the sensitivity of methods for the quantitation of TAAs both on the cell surface and in soluble form. To this end, different combinations and sequences of application of the 3 MAbs were used both in cell-surface binding experiments and in solid-phase radioimmunoassays. Results of this study show that only selected combinations of MAbs are capable of significantly improving the sensitivity of methods for HMW-MAA detection, and that such improvements depend on the order and mode of addition of the 3 reagents. Thus, mixtures of MAbs to distinct epitopes carried by a single TAA molecule are likely to increase the sensitivity of tests for tumor detection both in vitro (i.e. radioimmunoassays) and in vivo (i.e. immunoscintigraphy). However, because the binding properties of such mixtures do not simply reflect those of the individual reagents, protocols for the use of MAb cocktails should be critically evaluated before clinical use.

Animals↗
PubMed1987

Radioimmunodetection of neuroblastoma with antineuroblastoma monoclonal antibody.

The Antineuroblastoma monoclonal antibody CNM-5 was submitted to preclinical studies and then used for tumor imaging with following results. 1. CNM-5 is an antibody which belongs to the IgM fraction and has a molecular weight of 900 kilodaltons. Its protein concentration was found to be 17.99 mg/dl. 2. The 131I-labeled antibody was injected into nude mice transplanted with human neuroblastoma, and imaging was performed by a gamma camera. Accumulation of 131I in the tumor was relatively clearly seen. Various organs were removed and examined for 131I uptake. Radioactivity was easily detected in the tumor, suggesting that CNM-5 is effective for use in imaging diagnosis of neuroblastoma.

Animals↗
PubMed1986

Metabolizable 111In chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice.

The relative biological properties of 111In-labeled monoclonal antibodies (MoAb) coupled with a conventional bifunctional chelate (BC) and a new, enzyme metabolizable, bifunctional chelate (BCM) were investigated. A rat IgG2a MoAb against idiotype from a mouse B-cell lymphoma was utilized. Mice bearing B-cell lymphomas in the subcutaneous tissues of the flank were given IV-injections of labeled MoAb and imaged or killed for organ counting at 24 h or 48 h. Rat anti-dinitrophenyl IgG2a MoAb and non-specific polyclonal mouse IgG were used as controls. Compared to BC, the use of BCM resulted in a substantial decrease in blood background activity, a shorter biological half-life and an increase in tumor to blood ratio at the expense of a moderate decrease in absolute tumor uptake. The versatile chemistry of these C-1 substituted bifunctional chelates provides a variety of possible enzyme cleavable moieties for further investigation.

Animals↗
PubMed1986

A rat model system for radioimmunodetection of kappa myeloma antigen on malignant B cells.

A novel experimental model was established in normal rats for studying the localisation and tissue distribution of a murine monoclonal antibody directed against kappa light chain B cell malignancies. The antibody, K-1-21 was raised against human kappa Bence Jones Proteins and reacts with a cell membrane antigen KMA which is restricted to some kappa myeloma and lymphoma cells. In the rat model, kappa or lambda Bence Jones protein-conjugated sepharose was implanted subcutaneously on either flank 24 h before the injection of 131I-labelled K-1-21 or its F(ab')2 fragment. Gamma camera imaging and tissue distribution studies showed specific localisation of the K-1-21 antibody in the kappa sepharose. Injection of F(ab')2 antibody fragments resulted in faster background clearance, earlier delineation of the specific image and significantly higher target to blood ratios than those obtained with the intact antibody. These results suggest that the model may provide an alternative system to tumour xenograft bearing nude mice for studying localisation of antibodies with therapeutic potential.

Animals↗