A better control for ICD patients?
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Amiodarone↗
Biomedical subjects
T Ishimori
Publications and source records attributed to T Ishimori.
Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64).
DAB-Am64-(1B4M-Gd)(64) is a newly synthesized macromolecular liver magnetic resonance imaging (MRI) contrast agent with a polypropylenimine diaminobutane (DAB) dendrimer conjugated with a bifunctional diethylenetriaminepentaacetic acid (DTPA) derivative for complexing Gd(III) atoms. The characteristics of DAB-Am64-(1B4M-Gd)(64), which quickly accumulated in the liver, have been reported recently. In the present study, the dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was obtained in the mouse liver metastasis model using colon carcinoma cells to evaluate the ability to visualize the micrometastatic tumors compared with that using Gd-DTPA. The dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance the normal liver parenchyma and visualize micrometastatic tumors of 0.3-mm diameter in the liver of the mice with better contrast than that with Gd-DTPA. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a new liver MRI contrast agent potentially useful for diagnosis of micrometastasis in the liver.
Animals↗
Exposure of Caenorhabditis elegans to extremely low frequency high magnetic fields induces stress responses.
Responses of the small heat shock protein gene, hsp-16, were examined in transgenic Caenorhabditis elegans exposed to electromagnetic fields. Expression of the hsp-16-lacZ gene was enhanced when transgenic animals were exposed to magnetic fields up to 0.5 T at 60 Hz. The hsp-16 promoter was more efficiently expressed at the embryonic than at the post-embryonic stage irrespective of exposure. Promoter activity was more sensitive to the stimulus in the intestine at the post-embryonic stage. Evidence is presented that the induction occurs at the transcriptional step of hsp-16.
Animals↗
Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: accelerated renal excretion with coinjection of lysine.
One of the major limitations to macromolecular MRI contrast agents (MRI-CAs) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion of a macromolecular MRI-CA (generation-4 PAMAM dendrimer (G4D-(1B4M-Gd)64)) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D-dynamic-micro-MRI with G4D-(1B4M-Gd)64 was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B4M-Gd)64 increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D-(1B4M-Gd)64 from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(1B4M-Gd)64, when lysine was coinjected, the kidney-to-blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D-(1B4M-Gd)64 was excreted from the kidney intact.
Animals↗
3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent.
Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation-6 polyamidoamine dendrimer core (G6-(1B4M-Gd)192; MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies-KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma)-were used to obtain 3D MRA using G6-(1B4M-Gd)192 and Gd-DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 microm based on histology were visualized using 0.033 mmol Gd/kg of G6-(1B4M-Gd)192. In conclusion, intratumoral vasculature with a 100-microm diameter was visualized better using 3D MRA with G6-(1B4M-Gd)192 than with Gd-DTPA.
Animals↗
Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents.
Macromolecules conjugated with polyethylene glycol (PEG) acquire more hydrophilicity, resulting in a longer half-life in circulation and lower immunogenicity. Two novel conjugates for MRI contrast agents were synthesized from a generation-4 polyamidoamine dendrimer (G4D), 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M), and one or two PEG molecules with a molecular weight of 20000 Da (PEG(2)-G4D-(1B4M-Gd)(62) (MW: 96 kD), PEG(1)-G4D-(1B4M-Gd)(63) (MW: 77 kD)). Their pharmacokinetics, excretion, and properties as vascular MRI contrast agents were evaluated and compared with those of G4D-(1B4M-Gd)(64) (MW: 57 kD). PEG(2)-G4D-(1B4M-Gd)(62) remained in the blood significantly longer and accumulated significantly less in the liver and kidney than the other two preparations (P < 0.01). Although the blood clearance was slower, PEG(2)-G4D-(1B4M-Gd)(62) was excreted more readily without renal retention than the other two preparations. In conclusion, the positive effects of PEG conjugation on a macromolecular MRI contrast agent were found to be prolonged retention in the circulation, increased excretion, and decreased accumulation in the organs.
Animals↗
Novel liver macromolecular MR contrast agent with a polypropylenimine diaminobutyl dendrimer core: comparison to the vascular MR contrast agent with the polyamidoamine dendrimer core.
As MRI contrast agents, more hydrophobic molecules reportedly accumulate in the liver and thus are potentially useful as liver MRI contrast agents. In this study, a generation-4 polypropylenimine diaminobutane dendrimer (DAB-Am64), which is expected to be more hydrophobic than the generation-4 polyamidoamine dendrimer (PAMAM-G4D), was used to synthesize a conjugate with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M) [DAB-Am64-(1B4M-Gd)(64)] for complexing Gd(III) ions. This DAB conjugate quickly accumulated in the liver and its characteristics were studied and compared with those of a PAMAM conjugate [PAMAM-G4D-(1B4M-Gd)(64)], which is known to be a useful vascular MRI contrast agent, in regard to its availability as a liver MRI contrast agent. DAB-Am64-(1B4M-Gd)(64) accumulated significantly more in the liver and less in blood than PAMAM-G4D-(1B4M-Gd)(64) (P < 0.001). Contrast-enhanced MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance liver parenchyma and visualize both portal and hepatic veins of 0.5 mm diameter in mice. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a good candidate for a liver MRI contrast agent.
Animals↗
Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.
To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.
Animals↗
Hypopituitarism due to pituitary metastasis of lung cancer: case of a 21-year-old man.
A 21-year-old man presented persistent dry cough, general malaise, loss of appetite, decreased sexual desire and double vision. Chest radiograph revealed a mass shadow in the left upper lobe. Histopathological diagnosis of the tumor was squamous cell carcinoma. Brain computed tomography and magnetic resonance imaging revealed a metastasis to the pituitary gland. Hypopituitarism was diagnosed by pituitary function tests. Diabetes insipidus was absent and the function of the posterior lobe of the pituitary gland was preserved. Hypopituitarism due to pituitary metastasis is a rare complication of lung cancer, and has never been reported in a patient as young as 21 years old.
Adult↗
Clinical value of positron emission tomography with FDG for recurrent ovarian cancer.
OBJECTIVE: Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer. This prospective study was undertaken to evaluate the clinical contribution of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for recurrent ovarian cancer. SUBJECTS AND METHODS: Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study. Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements (group A). Clinical findings for the remaining 12 women showed them to be disease-free (group B). PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up. The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment. RESULTS: PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging, and treatment was affected in five patients. On the other hand, in group B, additional information was obtained in only three of 12 patients, and treatment of only one patient was affected. Overall sensitivity, specificity, and accuracy of conventional imaging modalities were 72.7%, 75.0%, and 73.3%, respectively, and these rates improved to 92.3%, 100.0%, and 94.4%, respectively, by considering both conventional imaging modalities and PET findings. CONCLUSION: Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer, especially patients believed to be at risk for recurrence.
Case-Control Studies↗
Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.
To establish an effective nonviral gene delivery and a corresponding imaging method for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were (111)In labeled through a diethylenetriaminepentaacetic acid chelate. (111)In-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. (111)In-oligo/G4-Bt and (111)In-oligo-Bt were conjugated to avidin ((111)In-oligo/G4-Av and (111)In-oligo-Av, respectively). (111)In-oligo/G4, (111)In-oligo/G4-Av, (111)In-oligo-Av, and carrier-free (111)In-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of (111)In-oligo-carrier complexes or (111)In-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after i.p. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of (111)In-oligo-carrier complex or (111)In-oligo (1.85 MBq/2.2 ng). (111)In-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of (111)In-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of (111)In-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver (111)In-oligo to i.p.-disseminated tumors. (111)In-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery.
Animals↗
Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.
For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.
Animals↗
FDG-PET of autoimmune-related pancreatitis: preliminary results.
The purpose of this retrospective study was to elucidate the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings in autoimmune-related pancreatitis (AIP), which is a reversible chronic pancreatitis with an autoimmune cause. The study group comprised six patients with clinically diagnosed AIP. After 370 MBq (10 mCi) of FDG had been injected intravenously, the abdomen and/or the whole body was scanned at 1 h post injection in all patients, and scanning was repeated at 2 h in four patients. PET findings were evaluated visually and/or semiquantitatively using the standardized uptake value (SUV). In four of the six patients, PET demonstrated intense uptake in the whole pancreas, which appeared swollen on computed tomography, and the accumulation increased with time in three patients. In one patient, intense focal uptake in the pancreatic head was observed, and the accumulation decreased over time. In the remaining patient, no abnormal accumulation in the pancreas was observed. Follow-up PET scanning after steroid therapy was performed in three patients, and intense FDG uptake was no longer observed. Our preliminary data show that AIP can cause intense FDG uptake in the pancreas. This fact, and the benign status of the condition, should be kept in mind when making a diagnosis with FDG-PET in patients with pancreatic disorders.
Cell Survival↗
Molecular genetic analysis of the Japanese amorph rh(null) phenotype.
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Humans↗
Pseudo-obstruction of the extrahepatic bile duct due to artifact from arterial pulsatile compression: a diagnostic pitfall of MR cholangiopancreatography.
PURPOSE: To evaluate the frequency of artifact from arterial pulsatile compression as the cause of pseudo-obstruction of the extrahepatic bile duct at magnetic resonance (MR) cholangiopancreatography (MRCP) and specify the causative vessels. MATERIALS AND METHODS: In 234 patients (102 men, 132 women; age range, 25-80 years), MRCP images obtained by using a single-shot turbo spin-echo sequence were reviewed to assess pseudo-obstruction of the extrahepatic bile duct caused by vascular compression. Dual-phase spiral computed tomography, contrast material-enhanced three-dimensional MR angiography, and/or digital subtraction angiography also were performed to determine the vessel that caused the pseudo-obstruction. RESULTS: Thirty-six pseudo-obstructions due to vascular compression were found in 33 (14%) patients. The common hepatic duct (27 [75%] sites) was the most common pseudo-obstruction site, followed by the left hepatic duct (four [11%] sites), proximal common bile duct (three [8%] sites), and right hepatic duct (two [6%] sites). The causative vessels were identified as the right hepatic artery at 24 (67%) sites; gastroduodenal artery, two (6%) sites; cystic artery, two (6%) sites; proper hepatic artery, one (3%) site; and an unspecified branch of the common hepatic artery, seven (19%) sites. CONCLUSION: At MRCP, pseudo-obstruction of the extrahepatic bile duct can be caused by pulsatile vascular compression of the hepatic and gastroduodenal arteries, and it should not be misdiagnosed as a bile duct tumor or biliary stone.
Adult↗
Scrotal disorders: evaluation of testicular enhancement patterns at dynamic contrast-enhanced subtraction MR imaging.
PURPOSE: To evaluate testicular enhancement patterns in various scrotal disorders at dynamic contrast medium-enhanced subtraction magnetic resonance (MR) imaging. MATERIALS AND METHODS: Forty-two patients with scrotal symptoms (22 testicular diseases, 20 extratesticular scrotal disorders) underwent three-dimensional (3D) fast field-echo or fast spin-echo dynamic subtraction MR imaging after injection of paramagnetic contrast medium. The relative percentages of peak height and mean slope of the testes on the affected side were compared with those on the unaffected side by using time-signal intensity curves. RESULTS: Extratesticular scrotal disorders (time-signal intensity curve mean peak height, 93.1%; mean slope, 89.8%) showed gradual and progressive increase in homogeneous testicular contrast enhancement in all normal testes. Relative percentages of peak height and mean slope of testicular torsion (mean peak height, 17.3%; mean slope, 10.6%), infarction (mean peak height, 30.4%; mean slope, 19.8%), traumatic hemorrhagic necrosis (mean peak height, -3.5%; mean slope, -12.0%), and epidermoid cyst (mean peak height, -6.6%; mean slope, -14.2%) were significantly lower than those of extratesticular scrotal disorders. Acute mumps orchitis (mean peak height, 135.1%; mean slope, 307.5%) and malignant testicular tumor (mean peak height, 178.7%; mean slope, 467.6%) showed higher relative percentages of peak height and mean slope. CONCLUSION: Dynamic contrast-enhanced subtraction MR imaging can provide information about testicular perfusion on the basis of contrast enhancement and can be used to differentiate testicular diseases from scrotal disorders.
Adolescent↗
Establishment and characterization of a breast cancer cell line expressing Na+/I- symporters for radioiodide concentrator gene therapy.
UNLABELLED: 131I therapy is a widely accepted treatment for metastatic differentiated thyroid cancer. To investigate the feasibility of 131I therapy for breast cancer, we established breast cancer cells stably expressing Na-/I- symporter (NIS) gene that can be modulated and studied in vitro and in vivo. METHODS: We transfected rat NIS genes into a human breast cancer cell line (MCF7) by electroporation. Iodide accumulation was evaluated under various extracellular concentrations of sodium and iodide, and iodide efflux was also assessed. Biodistribution and tumor imaging were studied using tumor-bearing mice. RESULTS: A novel cell line (MCF3B), stably expressing the NIS gene, was established from MCF7. MCF3B took up 44 times more radioiodide in vitro than MCF7 did. Iodide uptake was completely inhibited by 1 mmol/L perchlorate and was dependent on external sodium and iodide concentrations. Iodide efflux from MCF3B cells was slower (half-life [T 1/2] > 27 min) than from FRTL5 thyroid cells (T 1/2 = 4 min). In the biodistribution study using MCF3B-xenografted mice, high tumor uptake of 125I was shown (16.73%) at 1 h after injection, and tumor-to-normal tissue ratios were also high (4.84-21.28), except in the stomach (0.47). However, the iodide accumulation in the tumor lessened with time, reaching less than 1% at 24 h after injection. CONCLUSION: Our preliminary data indicate that NIS-based gene therapy may be applied by concentrating a lethal dose of radiation in tumor cells in vivo, but further investigation is necessary to determine a method of maintaining radioiodine in the cells to allow greater therapeutic effects.
Animals↗
Anomalies and anatomic variants of the biliary tree revealed by MR cholangiopancreatography.
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Adult↗