Immunoscintigraphy and pharmacokinetics of indium-111-labeled ZME-018 monoclonal antibody in patients with malignant melanoma.

Immunoscintigraphic and pharmacokinetic characteristics of 111In-labeled ZME-018 monoclonal antibody were examined in 8 patients with malignant melanoma. Each patient received a single intravenous infusion of 20 mg of ZME-018, coupled to 3 mCi of 111In without any acute toxicity. Scintigrams were taken 1, 3, and 6 days after the administration, and blood and urine samples were also taken frequently.

Semiquantitative in vitro binding assay of indium-111-labeled monoclonal antibodies to human cancer and normal tissues.

We have developed a simple in vitro method for the semiquantitative assessment of the radiolabeled antibody binding to cancer and normal tissues. Indium-111-labeled F(ab')2 fragments of 17-1A and 19-9 monoclonal antibodies with well-characterized specificity for gastrointestinal cancer demonstrated similar binding properties between cultured cancer cells and membrane fractions of homogenates prepared from tumor tissues. All of the 17 colon cancer specimens and seven (64%) of 11 gastric cancer specimens obtained by surgery showed positive binding with 17-1A.

67Ga-labeled antibodies for immunoscintigraphy and evaluation of tumor targeting of drug-antibody conjugates in mice.

To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with 67Ga, was conjugated with monoclonal antibodies using three different methods. One method used a homocoupling reagent, glutaraldehyde, whereas two other methods used heterocoupling reagents, N-succinimidyl-3-(2-pyridyldithio)propionate and succinimidyl-6-maleimidohexanoate, linking deferoxamine to antibodies through alkylamine, disulfide, and thioether bonds, respectively. Antibodies were efficiently labeled with 67Ga through chelation with deferoxamine without losing antigen-binding capability.

Relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled monoclonal antibodies.

The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using 125I- and 111In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies--OST6, OST7, and OST15--raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both 125I- and 111In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, 125I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than 125I-labeled OST7.

Recognition of ovarian cancer antigen CA125 by murine monoclonal antibody produced by immunization of lung cancer cells.

In studies aimed at developing monoclonal antibodies against lung adenocarcinomas, we produced a murine monoclonal antibody designated 130-22 by immunizing mice with lung cancer cells. Since in immunoperoxidase staining experiments this antibody was reactive not only with lung adenocarcinomas but also with ovarian carcinomas, we examined its relationship to the ovarian cancer marker CA125, an antigen recognized by monoclonal antibody OC125 produced by immunization of mice with ovarian carcinoma cells. Although CA125 antigen was adsorbed by 130-22 antibody, 125I-labeled 130-22 did not compete with OC125, indicating that although these two antibodies recognized CA125 antigen, they reacted with separate antigenic determinants.

Preparation of 67Ga-labeled antibodies using deferoxamine as a bifunctional chelate. An improved method.

Radionuclides or anti-cancer drugs may be coupled to antibodies for specific transport to target tissues. We have previously reported that several proteins could be rapidly and efficiently labeled with gallium (67Ga) by using deferoxamine (DFO) as a bifunctional chelating agent. In the present paper, we have described the use of hetero-bifunctional agents for the conjugation of DFO with antibodies and investigated the effect of coupling agents on in vitro properties and biodistribution of 67Ga-labeled antibodies.

Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.

Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined.

Localization of human osteogenic sarcoma xenografts in nude mice by a monoclonal antibody labeled with radioiodine and indium-111.

Monoclonal antibody OST7 reacts specifically with human osteogenic sarcoma. Whole immunoglobulin G (IgG) and the F(ab')2 fragment of OST7 were labeled with radioiodine and indium-111 (111I), and injected into athymic nude mice bearing xenografts of human osteogenic sarcoma (KT005). All radiolabels retained their antigen-binding activities allowing clear visualization of transplanted tumors.

Preparation and properties of antitumor monoclonal antibodies labeled with metallic radionuclides indium-111, gallium-67, and technetium-99m.

In this study, metallic radionuclides such as 111In, 67Ga, or 99mTc produced clear visualization in scintigraphic imaging of tumors; they have short half-lives and can easily be used in the radiolabeling of monoclonal antibodies by using bifunctional chelating agents. Under selected conditions, these radiolabeled antibodies were stable both in vitro and in vivo with no loss of the antigen-binding activity. Despite high background imaging of the liver and kidney, transplanted tumors in nude mice were clearly visualized with 111In-, 67Ga-, and 99mTc-labeled antibodies at 6, 24, or 48 hours after the injection.

Radioimmunoimaging of human bladder tumor xenografts in nude mice by using monoclonal antibodies.

Monoclonal antibodies HBJ127 and HBJ8, raised against T24 human bladder cancer cells, predominantly react with the cells in proliferating stages and with a portion of epithelial tumor cells, respectively. To investigate the in vivo localization of these monoclonal antibodies, the antibodies were labeled with radioiodine and indium-111 (111In) and injected into nude mice transplanted with human bladder tumors. The BT-11 bladder tumor had the highest concentration of radioiodinated HBJ127 and HBJ8 monoclonal antibodies, with 11.

[Analysis of serum CA125, CEA, AFP, LDH levels and LDH isoenzymes in patients with ovarian tumors--correlation between tumor markers and histological types of ovarian tumors].

Serum CA125, CEA, AFP, LDH levels and LDH isoenzymes were analyzed in ovarian tumor patients, who were treated at Kyoto University Hospital. CA125 was positive in 10/16 (62.5%) cases of common epithelial carcinoma, especially 100% positive in serous carcinoma, but was negative in mucinous tumors.

Computed tomography and 131I-MIBG scintigraphy in the diagnosis of pheochromocytoma.

In order to evaluate the usefulness of computed tomography (CT) and 131I meta-iodobenzylguanidine (131I-MIBG) scintigraphy for the localization of pheochromocytoma, a prospective study was undertaken in 23 patients with possible pheochromocytoma. Seventeen tumors were identified in 13 patients. Two tumors were extra-adrenal.

Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma.

Carbohydrate antigen (CA) 19-9 is a new tumor marker, defined by a monoclonal antibody. Serum CA 19-9 concentrations and computed tomography (CT) findings were studied in 55 patients with histologically proven adenocarcinoma, and in 22 patients with chronic pancreatitis. CA 19-9 was useful in 83% of cases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitis, and serum CA 19-9 levels in pancreatic carcinoma were highly related to the size of tumors.

[Sequential measurement of serum CA 125 levels in Krukenberg's tumor].

CA 125 is a tumor marker for ovarian cancer developed by hybridoma technology. In the present study, the levels of CA 125 were sequentially measured in the serum of five patients with Krukenberg's tumor originating in the gastrointestinal tract. Four out of the five (80%) had elevated serum CA 125 levels, i.

Imaging of head and neck tumors with technetium(V)-99m DMSA. A new tumor-seeking agent.

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging.