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Radioimmunodetection in rhabdo- and leiomyosarcoma with 111In-anti-myosin monoclonal antibody complex.

In patients with rhabdo- and leiomyosarcoma a radioimmunodiagnostic study was performed with 111In labeled F(ab) fragments of a monoclonal antibody against myosin. Eight patients with rhabdomyosarcoma and 18 patients with leiomyosarcoma were studied. Scanning was performed at 4, 24, and 48 h after administration of 74 MBeq of the antibody complex. A high uptake with a tumor:background ratio of 10:1 was observed in several patients with rhabdomyosarcoma but the results were less accurate in leiomyosarcoma.

Adolescent↗

[Experimental studies of the possibilities of radioimmunodetection of cancer of the large intestine by subcutaneous administration of iodinated antibodies to intestinal antigen beta1-MA].

131I- and 125I-labeled rabbit antibodies (AB) to the specific human intestinal beta 1MA were administered sc and iv to nude mice xenografts of human colon carcinoma. A study was made of the pharmacokinetics of labeled AB in the recipients' organs and tissues, measuring the radioactivity of tissue specimens on days 2, 3, 4 and 7 after injection with a gamma-counter, calculating specific radioactivity and accumulation indices. Tumors were visualized with a gamma-camera and a scanner. Proceeding from the comparison of the results of sc and iv administration of iodinated AB, a conclusion has been made of the applicability of sc injections of the agent for immunoscintigraphy.

Animals↗

Radioimmunodetection of prostatic cancer with 125I-labelled antibody against prostatic specific antigen.

A murine monoclonal antibody directed against human prostatic specific antigen was labelled with 125I and used in immunoscintigraphy studies of nude mice bearing xenografts of a human prostatic carcinoma cell line (DU-145). The antibody was injected intraperitoneally and the distribution was followed daily with the use of a gamma scintillation camera. Specific uptake was seen in the tumor, with optimal imaging 7-9 days after the injection of the radio-labelled antibody. Fab fragments of the radio labelled antibody were also investigated. These exhibited a strikingly shorter bio-distribution time, with optimal visualization of the tumor after 14-28 hours. Normal murine IgG and Fab fragments used in control experiments exhibited radioactivity that was comparable to that of normal tissue.

Animals↗

Reduction of background activities by introduction of a diester linkage between antibody and a chelate in radioimmunodetection of tumor.

A diester linkage was added between monoclonal anti-melanoma antibody 96.5 and a diethylenetriaminepentaacetic acid derivative to test if a tumor-to-blood and -to-organ ratio of the injected antibody in nude mice with human melanoma FEM XII xenografts could be increased by the addition of the readily cleavable linkage. Compared to the 111In-labeled antibody DTPA with a peptide linkage, the diester conjugate cleared much faster from the blood and was retained much less in muscle and normal organs such as liver, spleen and kidney over a 48-hr period. On the other hand, the activity retained in the tumor was larger than or similar to that of the peptide conjugate for this time period. This resulted in a 2.5, 2.1, and 2.6 fold increase in a tumor to blood, to liver and to kidney ratio at 48 hr for the diester conjugate as compared to the peptide conjugate. The whole-body biologic half life of the antibody was 36 hr, three times shorter than the peptide conjugate. The external imaging demonstrated a clearly visible tumor at 4 hr and a lower pool activity at 72 hr for the diester conjugate. The peptide conjugate, however, showed a persistant blood-pool activity at 72 hr. The addition of the diester linkage, therefore may be beneficial for imaging tumors in patients at early time intervals after injection.

Animals↗

Radioimmunodetection of human choriocarcinoma xenografts by monoclonal antibody to placental alkaline phosphatase.

Placental alkaline phosphatase (PLAP)-specific monoclonal antibody (MAb) 11-D-10, which did not react with other isoenzymes of alkaline phosphatase (AP), was raised by a hybridoma technique. MAb 11-D-10 was radiolabeled and administered to athymic mice bearing human choriocarcinoma containing PLAP. This antibody was found to be more specifically localized in tumor tissue as compared to normal tissues. The tissue-to-blood ratio (T/B ratio) of MAb 11-D-10 in tumor tissue increased from 1.38 at 2 days to 2.51 at 5 days after administration. On the other hand, the T/B ratios of isotype control non-immunized IgM in tumor tissue were 0.72 and 0.87 at 2 days and 5 days after administration, respectively. 131I-labeled MAb 11-D-10 was administered to athymic mice bearing choriocarcinomas of various sizes and various PLAP contents to examine the effect on the radioimage of the differences in tumor size and PLAP content. Tumors less than 0.3 cm in diameter could be imaged clearly by gamma-scintigraphy without blood pool image subtraction. The strength of the radioimage correlated fairly well with PLAP content.

Alkaline Phosphatase↗

Long-term persistence of human anti-murine antibody responses following radioimmunodetection and radioimmunotherapy of cutaneous T-cell lymphoma patients using 131I-T101.

Five cutaneous T-cell lymphoma (CTCL) patients have been imaged and treated with radiolabeled murine monoclonal antibody 131I-T101 in our laboratory. All patients developed human anti-murine antibody responses (HAMA) 14 days after the primary antibody infusion. HAMA responses could still be detected more than 22 months after T101 treatment. A substantial proportion of HAMA was crossreactive with any IgG2a antibody tested, although there did exist a specific anti-idiotypic component to HAMA. HAMA were of both IgM and IgG isotype. We also analyzed the effects of plasmapheresis on the specific HAMA isotypes in three patients who were retreated at the time of disease progression.

Aged↗

Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibody.

The purpose of the study was threefold: (1) to evaluate the efficacy of an 111In-labeled murine monoclonal antibody (ZME-018) directed against a heavy molecular weight melanoma associated glycoprotein in localizing metastatic disease; (2) to determine the effect of unlabeled antibody mass (2.5, 5, 10, 20, and 40 mg) on labeled antibody blood clearance, biodistribution and lesion detection; (3) to estimate radiation dosimetry. Twenty-five patients with previously documented disease received an intravenous infusion of 2.5 to 40 mg of monoclonal antibody with 1 mg of the antibody labeled with 5 mCi of 111In. There were no acute reactions. Patients were scanned without computer enhancement or background subtraction techniques at 24 and 72 hr after injection. Imaging detected tumor in 14/18 (78%) patients with active disease, identified 24/44 (77%) of lesions greater than 1 cm and changed or specifically directed patient management in 22% (4/18) patients with tumor. There was a prolongation in blood clearance associated with decreased liver and spleen activity following administration of 20 and 40 mg of antibody compared to the three lower antibody dose levels. Assuming a biodistribution similar to [111In]ZME-018, the radiation dose delivered to normal tissues by [90Y]ZME-018 would restrict its use as a routine vehicle for radioimmunotherapy; however, it may be possible to deliver substantial tumor doses in selected patients.

Adult↗

Anti-antibody enhancement of iodine-131 anti-CEA radioimmunodetection in experimental and clinical studies.

Imaging of tumors with radiolabeled antibodies, especially when located in the blood-rich visceral organs, may be improved through administration of a second antibody directed against the primary tumor-associated antibody. In hamsters bearing a human colonic carcinoma xenograft producing carcinoembryonic antigen (CEA), we injected donkey anti-goat IgG 24 hr after administration of 131I-labeled goat anti-CEA IgG and achieved enhanced tumor imaging 24-48 hr later, with a significant relative decrease of radioactivity in blood and all major organs except the spleen. In seven of nine patients, this method of anti-antibody clearance of nontargeted radioactive murine monoclonal antibodies revealed sites of cancer, including liver metastases. Characterization of radioactivity in the plasma before and after administration of the second antibody confirmed that complexes were quickly formed between primary and secondary antibodies, and imaging of the patients revealed a rapid uptake of radioactivity in the liver at 2 hr that dissipated within 24 hr. Radioactivity in the spleen gradually increased over time. The method of anti-antibody immunological enhancement of cancer imaging is feasible and may reveal tumor sites missed by conventional imaging.

Animals↗

Radioimmunodetection of human glioma xenografts by monoclonal antibody to epidermal growth factor receptor.

Murine IgG2a monoclonal antibody (MAb) 425 specifically detects epidermal growth factor receptor, which is expressed on human gliomas and tumors of other tissue origin but rarely on normal brain tissues, and not at all on bone marrow and peripheral blood cells. 131I-labeled F(ab')2 fragments of this MAb injected into nude mice grafted with U-87 MG glioma cells preferentially localized in tumor tissue compared to normal mouse tissues, as determined by differential tissue counting of radioactivity. The mean tumor-to-tissue ratios of radioactivity ranged between 8.2 (blood) and 55.8 (muscle) at 2 days after the injection of 15 muCi of 131I-425 F(ab')2/mouse. Radiolabeled fragments of an anti-hepatitis virus IgG2a MAb did not localize in tumors. The localization index derived from the ratios of specific antibody to indifferent antibody in tumor tissue relative to blood was 9.94 at 2 days following the MAb injection. The labeled MAb did not localize in a xenograft of colorectal cancer tumor, which does not express the epidermal growth factor receptor. Tumors could be located by whole-body gamma-scintigraphy without background subtraction following the injection of 100 muCi of radiolabeled MAb 425 F(ab')2 fragments. The data suggest that MAb 425 is a likely candidate for clinical diagnostic and radioimmunotherapy trials.

Animals↗

[Radioimmunodetection of human colonic cancer transplanted into thymus-deficient mice using antibodies to the intestinal antigen].

131I-antibodies (Ab) to human organ-specific intestinal antigen--beta 1-MA (maconial antigen) were injected intravenously to nude mice to whom various human tumors including colon tumors had been transplanted. Ab distribution in recipient tissues and in tumors was determined over time with the help of a gamma-counter. Ab to beta 1-MA was shown to localize specifically in colon tumors. 131I-Ab accumulation in this tumor exceeded the background level in tumor-bearing tissues. The excess increased with time as a result of slower Ab clearance of colon tumors as compared to normal tissues. beta 1-MA was detected immunohistochemically in the mouse colon epithelium however elevated accumulation of Ab to beta 1-MA injected into the blood flow in the intestine was undetectable.

Animals↗