The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

Superconducting tunnel junctions have potential high energy-resolution for X-ray detection. The excellent performance may be suited for experiments making use of X-rays from a synchrotron radiation. The characteristics of the Nb-based junction were studied to know the response of Nb-based junctions to the synchrotron radiation. We obtained the dependence of the detector pulse height on X-ray energies in a range of 4 to 15 keV.<>

We placed a Gianturco self-expanding metallic stent across the recurrent stricture of an esophagojejunostomy in a patient with gastric cancer. Though excellent passage of food resulted, intractable reflux occurred. Two months later the patient succumbed to recurrent tumor. At autopsy, the stent was patent and was partially covered by esophageal mucosa. There were narrow but deep ulcers around the stent hooks. The Gianturco metallic stent may provide an additional option for treating recurrent enteric strictures after other methods fail. Further refinements of the technique appear necessary.

Dual x-ray absorptiometry (DXA) (Hologic QDR-1000/W; Hologic, Inc.) was used to measure lumbar vertebral bone mineral density (BMD) in 83 healthy Japanese infants and children (55 boys and 28 girls) aged 0–17 years, and the values obtained were correlated with age, body weight and body height. The lumbar BMD (average of L1–L4 values) increased with age, with a nearly twofold increase found from preschool age to adolescence. It also increased with body weight and body height. Our results on normal Japanese infants and children appear almost similar to those reported in French and American studies. Because of its great precision and accuracy, low radiation exposure and rapid scanning, DXA may be the most suitable for use in infants and children. With normal Japanese data now available with this technique, pediatricians can better detect metabolic bone diseases in infants and children and follow the bone response to medical intervention in patients with these conditions.

Herein we report an infantile case of congenital hydrocolpos combined with left renal agenesis which presented with an abnormal mass protruding from the vaginal introitus. The diagnosis was made shortly after birth by ultrasonography and confirmed by other radiologic diagnostic methods. This case highlights the value of ultrasonography in diagnosing hydrocolpos and determining the coexistence of renal anomalies.

The case is presented of a four year old boy with a large left abdominal mass. The patient was diagnosed as having a left giant hydroureteronephrosis due to a primary obstructed megaureter, based on the findings of ultrasonography, micturating cystourethrography, excretion urography, computed tomography and percutaneous antegrade pyeloureterography. Diuretic renography showed that the obstruction was partial. Since a static renal scintigram indicated that renal function on the affected side was moderately well preserved, ureteroplasty is planned.

Using dual‐energy x‐ray absorptiometry (DEXA), the lumbar spinal bone mineral density (BMD) in 49 Japanese children with or without metabolic bone disease (MBD) was determined. The following results were obtained: (a) The normal data for healthy Caucasians (J Clin Endocrinol Metab 1990; 70: 1330‐1333) appear to be applicable to Japanese children; (b) BMD was normal in patients with congenital hydronephrosis with normal renal function; (c) One patient with congenital renal failure and one with Lowe syndrome had low BMD, but the MBD in the former improved markedly with peritoneal dialysis; (d) A reduced BMD was found in patients treated with long‐term steroids, probably because of decreased turnover of bone; (e) A reduction in BMD was pronounced in preterm infants during the first few months of life. In conclusion, DEXA is a useful method of bone densitometry in MBD in children.

We generated five murine monoclonal antibodies reactive with ovarian cancer-associated antigen CA125. These monoclonal antibodies seemed to bind to separate epitopes from OC125 antibody, known to recognize CA125. A series of im-munoradiometric assays for measuring serum CA125 values rapidly and sensitively were devised using these monoclonal antibodies. The antigenic determinant of a new immunoradiometric assay was different from that of a currently used CA125 kit employing OC125 both as a catcher and a tracer. However, serum antigen levels were closely correlated to each other and were elevated not only in patients with ovarian cancer, but also in patients with endometriosis and in some normal females during menstruation. These results suggest that CA125 has at least two antigenic determinants close to each other and this new rapid assay is useful, although not specific for ovarian cancer, in patients with gynecological disorders.

The presence of cancer-associated antigens CA125, CA19-9, and carcinoembryonic antigen (CEA) in apparently normal respiratory system was demonstrated histochemically and immunochemically. Epithelial cells lining central airways (trachea, bronchi, and bronchioli) and respiratory glands were specifically stained by antibodies recognizing CA125, CA19-9, and CEA. Most, if not all, bronchial mucus obtained from patients without pulmonary diseases during general anesthesia contained remarkably high levels of CA125, CA19-9, and CEA ranging from 190 to 41,000 U/ml (594-4803 U/mg protein), 210 to 95,000 U/ml (294-197,917 U/mg protein), and 6 to 940 ng/ml (14-209 ng/mg protein), respectively, whereas serum antigen levels were normal in all cases examined. These results suggest that CA125, CA19-9, and CEA are synthesized and secreted by normal epithelial cells of central airways and/or respiratory glands and that these substances are not specific indicators of abnormal cellular activity.

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. 67Ga-labeled antibodies clearly visualized transplanted tumors in nude mice. However, the biodistribution of radioactivity was markedly different with the coupling methods used for the conjugation of deferoxamine and antibodies. High nonspecific uptake in the liver and spleen was observed with 67Ga-labeled antibodies prepared by the glutaraldehyde method. 67Ga-labeled antibodies linked by thioether bonds demonstrated in vivo stability and the highest tumor:liver ratio, whereas 67Ga-labeled antibodies conjugated with disulfide bonds were rapidly cleared from the circulation. These results indicate that antibody conjugates linked by thioether bonds are a better choice for drug targeting and that 67Ga-labeled antitumor monoclonal antibodies are useful not only for the immunoscintigraphy but also for the quantitative assessment and visualization of the biodistribution of drug-antibody conjugates.

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.

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. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of 111In-labeled OST6 was higher, although not significantly, than that of 111In-labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either 125I or 111In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding.

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. Although tissue distribution in the liver, kidney, and bone was different among radionuclides used for the labeling, all tumor to blood ratios were higher than those of radioiodinated monoclonal antibodies. These results provide a good basis for studies of the clinical usefulness of 111In-, 67Ga-, and 99mTc-labeled monoclonal antibodies for radioimmunoimaging.

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. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.

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. The antigen defined by both antibodies was thought to be heat-labile glycoprotein with a molecular weight of over 1,000,000. A series of immunoradiometric assays was developed using combinations of two monoclonal antibodies in a simultaneous forward sandwich mode. Mixed monoclonal antibodies may provide a more sensitive assay for the detection of CA125 than the homologous assay, in which OC125 was used both as a tracer and as a catcher. These results indicate that CA125 is an antigen with two separate epitopes present in both ovarian and lung adenocarcinomas and that combination use of monoclonal antibodies reactive with different antigenic determinants will give certain advantages to the immunoradiometric assay of cancer markers.