No abstract available

[en] Radioimmunolocalization of an ¹¹¹In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single. i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi ¹¹¹In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel, testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p less than 0.005). A significant correlation was observed between tumor uptake of ¹¹¹In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T1/2 of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of ¹¹¹In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with ¹¹¹In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site

[en] The media of representative mammalian cell lines were supplemented with low levels of selenium in the form of sodium selenite in order to investigate the effects of selenium on mammalian cells. Following incubation in 30 nM sodium selenite, these cells were assayed for changes in glutathione peroxidase (GPx) activity. The cells examined included NIH 3T3 mouse fibroblasts, PC12 rat sympathetic precursor cells, SupT-1 human lymphocytes, MCF-7^adr human breast carcinoma cells and AA8 Chinese hamster ovary cells. Selenium supplementation resulted in a marginal increase in GPx activity for the NIH 3T3, MCF-7^adr and Supt-1 cells but stimulated GPx activity approximately 5-fold in PC12 and AA8 cells. AA8 cells were selected to evaluate whether selenium supplementation was radioprotective against ⁶⁰cobalt gamma irradiation. Protection against radiation-induced mutation was measured by evaluating mutation frequency at the hprt locus. In this assay, preincubation of AA8 CHO cells significantly protected these cells from exposure to 8 Gy

[en] The authors studied the effect of varying chase doses of unlabeled nonimmunoreactive subspecies of 96.5 antimelanoma monoclonal antibody (Mab 96.5a) on the pharmacokinetics and body distribution of In-111-labeled 1-mg pulses of immunoreactive Mab 96.5 given intravenously 1 hour later. Results were compared with their phase III findings of varying doses of unlabeled immunoreactive 96.5 Mab coinfused with 1 mg of In-111. Pharmacokinetics showed a two-phase blood clearance. Alpha phase t1/2 rose from 4+- 1.7 min at 9 mg to 15 +- 8 min at 19 mg. Beta phase t1/2 rose from 1,795 to 2,806 min respiration. Body distribution showed high liver uptake visually and by regions of interest (e.g., liver/heart ratio of 9.25, vs. 2.76 in phase III coinfusion study). Lesion detection was not significantly different from what was seen in the phase III study. This lack of liver blockage by nonimmunoreactive 96.5a may indicate that liver localization of 96.5 is not dependent on nonspecific binding to reticuloendothelial cells by the Fc fragment (common to both subspecies). Partial saturation of specific antigenic sites may be the factor in liver blockage

[en] 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. 163 references

No abstract available

[en] A radiolabeled monoclonal antibody (96.5) reactive with an Mr 97,000 antigen found on over 80% of melanoma cell lines and tissue extracts was examined for its ability to detect malignant melanoma metastases in vivo. For imaging purposes, it was conjugated with diethyltriaminepentaacetic acid and subsequently labeled with ¹¹¹In by chelation. Thirty-one patients with metastatic melanoma received single injections of monoclonal antibody 96.5 at concentrations ranging from 0.5 to 20 mg and at specific activities of ¹¹¹In ranging from 0.125 to 4 mCi/mg. Total-body scans were performed at various time intervals following administration. No serious side effects were observed. Of a total of 100 previously documented metastatic sites, 50 imaged for a specificity of 50%. The number of sites imaged increased significantly as the amount of antibody administered increased relative to the average radiation dose. Considerable background uptake of isotope was observed in blood pool and other organs with gradual acquisition of label in tumor sites by 48 to 72 h. Hence, tumor imaging of melanoma using ¹¹¹In-labeled monoclonal antibody 96.5 appeared feasible, especially at antibody doses above 2 mg

[en] The authors have studied 20 patients with either metastatic ocular melanoma or disseminated cutaneous melanoma, using Tc-99m monoclonal antibody Fab to the Gp 240d antigen. Patients were preinjected with blocking doses of unlabeled antibody. Ten milligrams of Fab was labeled with 10-25 mCi of TcO/sub 4/. One hundred seventy-two lesions were known, and 136 were detected (sensitivity, 79%). Liver metastases detection was excellent, and the sensitivity was 100% for ocular lesions and for splenic metastases. Only two of ten lesions under 1 cm were detected. Region of interest analysis revealed high renal uptake of labeled Fab at 8 hours but relatively higher lung uptake at 24 hours. Single photon emission computed tomography detected five lesions in liver and skin not seen with planar imaging. Tc-99m antimelanoma NRX 118.07 has a potential in the management of patients with metastatic melanoma

[en] Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: (1) additional tumor sites could be imaged with the combination compared to a single Mab; (2) the first MAb influenced the biodistribution and tumor localization of the second; and (3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody

No abstract available