Biomedical subjects

Junji Konishi

Publications and source records attributed to Junji Konishi.

66 records · Page 4Linked to original sources

PubMed2002

Synthesis and evaluation of a monoreactive DOTA derivative for indium-111-based residualizing label to estimate protein pharmacokinetics.

The purpose of this study was to develop an indium-111 (111In)-based residualizing label for estimating the pharmacokinetics of proteins. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), which produced a highly stable and hydrophilic 111In chelate, was selected as the chelating site, and the monoreactive DOTA derivative with a tetrafluorophenyl group as the protein binding site (mDOTA) was designed to avoid cross-linkings of proteins. mDOTA was synthesized with an overall yield of 11%. The stability in murine plasma, the radioactivity retention in the catabolic sites of proteins and the radiochemical yields of 111In-labelled proteins via mDOTA were investigated using human serum albumin (HSA), galactosyl-neoglycoalbumin (NGA) and cytochrome c (cyt c) as model proteins. 111In-labelled HSA via mDOTA was highly stable for 5 days after incubation in murine plasma. Long retention of radioactivity in the catabolic sites was observed after injection of 111In-DOTA-NGA in mice, due to the slow elimination of the radiometabolite from the lysosome. At a chelator concentration of 42.2 microM, 111In-DOTA-cyt c was produced with over 91% radiochemical yield. On the other hand, 111In-DOTA-lysine and 111In-DOTA were obtained with high radiochemical yields at lower chelator concentrations. These findings indicated that mDOTA would be an appropriate 111In-labelling agent for estimating protein pharmacokinetics. These findings also suggested that the introduction of a protein binding site at a position distal from the unmodified DOTA structure would be preferable to preparing 111In-DOTA-labelled proteins with higher specific activity.

Animals↗

PubMed2002

Benign hepatic nodules in Budd-Chiari syndrome: radiologic-pathologic correlation with emphasis on the central scar.

OBJECTIVE: The purpose of this study was to determine the imaging features of benign hepatic nodules in patients with Budd-Chiari syndrome and to correlate them with pathologic findings, with special attention placed on the presence of a central scar. MATERIALS AND METHODS: Imaging findings of 59 benign hepatic nodules in four patients with chronic Budd-Chiari syndrome were analyzed retrospectively, and radiologic- pathologic correlation was performed in three patients with 50 hepatic nodules who underwent liver transplantation. All patients underwent multiphasic helical CT. In three patients with 29 lesions, MR imaging, including a multiphasic dynamic study, was performed. The CT and MR imaging findings in these patients were compared with those of 103 small hepatocellular carcinomas in 56 other patients (54 of them displayed chronic hepatitis or liver cirrhosis associated with viral hepatitis but none had Budd-Chiari syndrome). Image analysis was performed by two radiologists with no knowledge of the diagnosis. RESULTS: All patients with Budd-Chiari syndrome exhibited multiple benign nodules up to 3 cm in diameter, and 42 of 59 lesions were hypervascular. Microscopically, 15 of 32 nodules demonstrated a central scar; moreover, some nodules closely resembled focal nodular hyperplasia. Frequencies of hyperintensity on T1-weighted images (14/29 vs 25/103), hypointensity on T2-weighted images (7/29 vs 1/103), and the presence of a central scar (6/59 vs 1/103) were significantly higher in benign nodules than in hepatocellular carcinomas (p < 0.05; Fisher's exact test). Moreover, for lesions larger than 1 cm, imaging studies revealed a central scar in six of 15 benign lesions. CONCLUSION: Benign hepatic nodules in patients with in Budd-Chiari syndrome are usually small, multiple, and hypervascular. The presence of a central scar is a characteristic feature in those larger than 1 cm in diameter.

Adolescent↗

PubMed2002

Large coalescent parenchymal nodules in pulmonary sarcoidosis: "sarcoid galaxy" sign.

OBJECTIVE: The purpose of this study was to evaluate the large parenchymal nodules in pulmonary sarcoidosis and to describe a new CT sign termed the "sarcoid galaxy." CONCLUSION: The CT appearance of pulmonary sarcoidosis suggests that the large nodules arise from a coalescence of small nodules. The large nodules are surrounded by many tiny satellite nodules. These findings were considered to simulate the appearance of a galaxy. This observation was supported by radiologic-pathologic correlation. The sarcoid galaxy sign may be a useful adjunct in the diagnosis of pulmonary sarcoidosis.

Adult↗

PubMed2002

Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer.

UNLABELLED: Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter. METHODS: Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized uptake value (SUV) of the pancreatic cancer was determined, and the retention index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5-point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-HK-II and anti-GLUT-1 antibody (HK-index and G-index, respectively). RESULTS: SUV2 (mean +/- SD, 5.7 +/- 2.6) was higher than SUV1 (5.1 +/- 2.1), with an RI of 8.5 +/- 11.0. Four cases of cancer, in which SUV2 showed a decline from SUV1, showed a low HK-index (1.8 +/- 1.1), whereas 4 cases with an RI of > or =20 and 13 cases with an intermediate RI (0-20) showed significantly higher HK-indices (4.3 +/- 0.7 and 3.1 +/- 1.5, respectively; P < 0.05). RI showed a positive correlation with HK-index, with an R(2) of 0.27 (P < 0.05), but no significant correlation with the G-index. SUV1 showed no relationship with the HK-index but showed a weak positive correlation with the G-index, with an R(2) of 0.05 (P = 0.055). CONCLUSION: These preliminary findings suggest that the RI obtained from dual-phase (18)F-FDG PET can predict HK-II expression and that the SUV (at 1 h) has a positive correlation with GLUT-1 expression but not with HK-II expression.

Adenocarcinoma↗

PubMed2002

Increased (18)F-FDG uptake in a model of inflammation: concanavalin A-mediated lymphocyte activation.

UNLABELLED: The aim of this project was to study a mechanism that might explain the increased uptake of (18)F-labeled FDG seen in inflammation. The approach chosen was to examine the effect on (18)F-FDG uptake of acute activation of murine lymphocytes by concanavalin A (Con A). METHODS: Immunocompetent BALB/c mice and nude mice received an intravenous injection of 10 mg/kg Con A. Twenty-four hours later, the mice received an intravenous injection of 0.74 MBq (20 microCi) (18)F-FDG. One hour later, biodistribution was determined. The distribution of the radiolabel in the liver was also evaluated by autoradiography. In vitro (18)F-FDG uptake to splenocytes from BALB/c mice with and without Con A pretreatment were determined 30, 60, and 120 min after the splenocytes were mixed with (18)F-FDG (0.74 MBq [20 microCi]/200 microL). RESULTS: In immunocompetent BALB/c mice, pretreatment with Con A significantly increased (18)F-FDG uptake in the spleen and liver. Autoradiographs of the liver showed that pretreatment with Con A produced a specific localization of (18)F-FDG at periportal areas, where numerous sites of cellular infiltration were observed. In vitro binding of (18)F-FDG to the splenocytes was significantly higher for Con A-pretreated BALB/c mice than for control mice. CONCLUSION: This study showed that Con A increased (18)F-FDG uptake. Con A-activated lymphocytes actively took up (18)F-FDG both in vitro and in vivo, and (18)F-FDG specifically accumulated in Con A-mediated acute inflammatory tissues.

Animals↗

PubMedDate not supplied

Differential uptake of (18)F-fluorodeoxyglucose by experimental tumors xenografted into immunocompetent and immunodeficient mice and the effect of immunomodification.

PURPOSE: To study the contribution of immunologic background to the uptake of fluorine-18-fluorodeoxyglucose ((18)F-FDG) by the tumor tissues. METHODS: The uptakes of (18)F-FDG to the same experimental tumor model (SCCVII) xenografted into immunocompetent and immunodeficient (athymic) mice were compared. In addition, the immunomodifying effect of steroid on the uptake of (18)F-FDG by these tumors was investigated. RESULTS: The uptake of (18)F-FDG by the tumors in immunocompetent mice was significantly higher than that in immunodeficient (athymic) mice. Although steroid pretreatment had no effect on the tumor uptake in immunodeficient mice, it significantly decreased the tumor uptake in immunocompetent mice. CONCLUSION: The higher tumor uptake of (18)F-FDG observed in immunocompetent mice, modulated by steroid pretreatment, was contributed by the host immune reaction, probably cellular immunity employed by T-lymphocytes. These findings can clinically conclude that the intense accumulation of (18)F-FDG in the metastatic lymph nodes, which contain only a small number of cancer cells, was caused by the enhanced uptake of (18)F-FDG by activated T-lymphocytes due to host immunity against cancer cells present in metastatic lymph nodes.

Animals↗

PubMedDate not supplied

Control of radioactivity pharmacokinetics of 99mTc-HYNIC-labeled polypeptides derivatized with ternary ligand complexes.

An enhancement of the target/nontarget ratio of radioactivity levels enables reliable diagnosis and therapy using polypeptide radiopharmaceuticals in nuclear medicine. In the present study, we investigated the effects of the physicochemical properties of radiometabolites on the radioactivity pharmacokinetics after administration of 99mTc-labeled polypeptides using 6-hydrazinopyridine-3-carboxylic acid (HYNIC). Four ternary ligands (L) [3-benzoylpyridine (BP), 3-acetylpyridine (AP), 3-nicotinic acid (NIC), pyridine (PY)] with different lipophilicity were selected as coligands for the preparation of 99mTc-HYNIC-polypeptides. Each of the ternary ligands tested provided 99mTc-HYNIC-labeled galactosyl-neoalbumin (NGA) and Fab fragments of high stability with high radiochemical purity. Moreover, after administration of each 99mTc-HYNIC-labeled NGA into normal mice, the respective ternary ligand [99mTc](HYNIC-lysine)(tricine)(L) complexes were generated as final radiometabolites in the hepatic lysosome. The partition coefficients of [99mTc](HYNIC-lysine)(tricine)(BP), [99mTc](HYNIC-lysine)(tricine)(AP), [99mTc](HYNIC-lysine)(tricine)(NIC), and [99mTc](HYNIC-lysine)(tricine)(PY) were determined to be -2.21, -2.37, -2.93, and -2.73, respectively. Elimination rates of these radiometabolites from the lysosome were enhanced in the order of increasing lipophilicity of the radiometabolites. After injection of the four 99mTc-HYNIC-labeled Fab fragments into normal mice, blood clearances of radioactivity were similar while radioactivity elimination rates from the kidney were enhanced in the order of increasing lipophilicity of the radiometabolites. The present study indicated that the lipophilicity of the radiometabolites constitutes one important factor affecting their elimination rates from the tissues. Thus, as ternary ligands facilitate alteration of the physicochemical properties of radiometabolites, the use of ternary ligand complexes might be applicable for controlling the pharmacokinetics of 99mTc-labeled polypeptides.

Albumins↗

PubMedDate not supplied

Quantitative fluorine 18 deoxyglucose uptake by myocardial positron emission tomography in rats.

BACKGROUND: In vivo quantitative assessment of positron emission tomography (PET) with 2-deoxy-2-[fluorine 18]fluorodeoxyglucose (FDG) for rat heart has not been explored because of the theoretical limitation of spatial resolution. Our objective was to assess whether FDG uptake measured by PET is correlated with tissue radioactivity of FDG in rat heart directly measured by an automated gamma counter. METHODS AND RESULTS: Ten Sprague-Dawley rats were used for echocardiographic assessment and FDG-PET. Rats were sacrificed immediately after PET scanning, and the radioactivity of FDG in 4 segmental tissue samples of the middle transverse section was measured. Quantitative PET values in a total of 40 regions of interest, in which partial volume effect was corrected based on the phantom study and wall thickness obtained by echocardiogram, were compared with radioactivity of the corresponding 40 tissue samples. Linear regression analysis revealed that tissue radioactivity of FDG was well correlated with the quantitative PET value (Y = 1.17X; r = 0.985, P <.0001). CONCLUSIONS: Quantitative FDG-PET for rat heart is a reliable approach for assessing glucose metabolism in vivo after correction is made for partial volume effect. These results can be used for various models of heart disease with repeated studies over the disease process in the same animal.

Animals↗

PubMedDate not supplied

MR imaging of müllerian mucinous borderline tumors arising from endometriotic cysts.

This report describes MR findings of müllerian mucinous borderline tumors, pathologically proven to have arisen from endometriotic cysts, in three patients. They were unilocular or paucilocular masses with mural nodules. Cystic components showed hyperintensity on both T1- and T2-weighted images, simulating clear cell or endometrioid carcinomas arising from endometriotic cysts. Mural nodules showed prominent high signal intensity on T2-weighted images. Correlation with pathologic findings suggests that this hyperintensity reflects intraluminal mucinous material and stromal edema.

Adult↗

PubMedDate not supplied

Retained products of conception masquerading as acquired arteriovenous malformation.

This case documents a seldom-described event of retained products of conception masquerading as an acquired arteriovenous malformation (AVM) of the uterus. The patient presented with sudden onset of heavy vaginal bleeding 6 weeks after artificial abortion. Ultrasonography and magnetic resonance imaging revealed a diffuse intramural lesion predominantly consisting of prominent vessels, which raised suspicion of an AVM. Hysterectomy revealed retained products of placenta that were necrotic and encroached into thin myometrium.

Adult↗

PubMedDate not supplied

Primary cardiac lymphoma demonstrated by delayed contrast-enhanced magnetic resonance imaging.

Delayed contrast-enhanced magnetic resonance (MR) imaging that nullifies the signal of normal myocardium produces great differences in myocardial signal intensity between normal and infarcted myocardium. A case of primary cardiac lymphoma is presented in which delayed contrast-enhanced MR imaging clearly identified the localization and extension of a lymphoma infiltrating the myocardium.

Contrast Media↗

PubMedDate not supplied

Transcatheter arterial embolization for bleeding from bile duct tumor thrombi of hepatocellular carcinoma.

BACKGROUND/AIMS: Advanced hepatocellular carcinoma usually invades the portal vein, forming tumor thrombi. Invasion of the bile duct, i.e., intrabile tumor growth or bile duct tumor thrombi is rare. Patients with bile duct tumor thrombi present with obstructive jaundice, abdominal pain or hemobilia. Hemobilia due to bile duct tumor thrombi is sometimes massive and fatal. The purpose of our study was to evaluate the effectiveness of transcatheter arterial embolization for hemobilia caused by bile duct tumor thrombi of hepatocellular carcinoma. METHODOLOGY: Between 1993 January and 2000 December, transcatheter arterial embolization was performed in 4 patients with hemobilia and gastrointestinal bleeding from bile duct tumor thrombi of hepatocellular carcinoma. RESULTS: In all 4 patients, transcatheter arterial embolization was successfully performed and resulted in cessation of bleeding. One patient had recurrent hemobilia, which was controlled by another transcatheter arterial embolization. Three patients were discharged from hospital after transcatheter arterial embolization. Patients died of hepatic failure or multiple tumors 5 to 7 months after the onset of hemobilia, although hemobilia had been fully controlled. CONCLUSIONS: Transcatheter arterial embolization seemed to be effective for the control of massive hemobilia caused by bile duct tumor thrombi associated with hepatocellular carcinoma.

Aged↗