Publications (36)106.23 Total impact
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Article: 18F-FDG and 11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy.
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ABSTRACT: This study was performed to investigate the feasibility of FDG- and L-[methyl-11C]methionine (Met)-PET for the follow up of lung cancer after stereotactic radiotherapy (SRT). Nine patients (pt) with solitary lung cancer underwent SRT. Met- and FDG-PET studies were performed one week before SRT and from one week to 8 months after SRT. Responses to SRT were complete in 2 pt and partial in 7 pt. Met- and FDG-PET scan showed high tracer uptake in all tumors before SRT. After SRT, standardized uptake values (SUV) of FDG and Met changed concordantly. Both decreased with time in 5 pt but did not decrease steadily in 4 pt, where 2 pt showed an increase at 1 to 2 weeks after SRT and 2 pt showed an increase at more than 3 months after SRT. The former appears to reflect the acute reaction to SRT and the latter radiation-induced pneumonitis. Although the addition of Met-PET did not provide additional information over FDG-PET, FDG- and Met-PET could be used to evaluate the treatment effect of SRT.Annals of Nuclear Medicine. 01/2004; -
Article: Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) --usefulness and limitations in "clinical reality".
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ABSTRACT: The present review will provide an overview of the literature concerning the FDG PET diagnosis of pancreatic cancer and a summary from our experience of 231 cases of pancreatic lesions. FDG PET can effectively differentiate pancreatic cancer from benign lesion with high accuracy. Newly-developed PET scanners can detect small pancreatic cancers, up to 7 mm in diameter, by their high resolution, which could make a great contribution to the early detection of resectable and potentially curable pancreatic cancers. FDG PET is useful and cost-beneficial in the pre-operative staging of pancreatic cancer because an unexpected distant metastasis can be detected by whole-body PET in about 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. However, there are some drawbacks in PET diagnosis. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. As for false-positive cases, active and chronic pancreatitis and autoimmune pancreatitis sometimes show high FDG accumulation and mimic pancreatic cancer with a shape of focal uptake. There were 8 false negative cases in the detection of pancreatic cancer by FDG PET, up to 33 mm in diameter, mainly because of their poor cellularity in cancer tissues. In addition, there are 19% of cancer cases with a decline in FDG uptake from 1 hr to 2 hr scan. FDG PET was recently applied to and was shown to be feasible in the differential diagnosis of cystic pancreatic lesions, such as intraductal papillary mucinous tumor of the pancreas. Further investigations are required to clarify the clinical value of FDG PET in predicting prognosis of the pancreatic patients.Annals of Nuclear Medicine. 01/2003; -
Article: Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer.
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ABSTRACT: OBJECTIVE: The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated. METHODS: Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient. RESULTS: In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient's follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses. CONCLUSIONS: These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient.Annals of Nuclear Medicine. 01/2003; -
Article: Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.
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ABSTRACT: 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.Clinical Cancer Research 12/2001; 7(11):3606-12. · 7.74 Impact Factor -
Article: Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.
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ABSTRACT: 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.European Journal of Cancer 08/2001; 37(11):1429-34. · 5.54 Impact Factor -
Article: Clinical value of positron emission tomography with FDG for recurrent ovarian cancer.
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ABSTRACT: 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. 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. 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. 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.American Journal of Roentgenology 07/2001; 176(6):1449-54. · 2.78 Impact Factor -
Article: 3D-micro-MR angiography of mice using macromolecular MR contrast agents with polyamidoamine dendrimer core with reference to their pharmacokinetic properties.
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ABSTRACT: Four novel macromolecular MRI contrast agents, all of which had the same chemical composition but different molecular weights, were prepared using generation-3, -4, -5, and -6 polyamidoamine (PAMAM) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size-dependent changes in the pharmacokinetics were observed in the biodistribution study. (153)Gd-labeled generation-6 PAMAM-conjugates remained in the blood significantly longer than all of the other preparations (P < 0.001). The increase in blood-to-organ ratio of the preparations was found to correlate with increasing molecular size (P < 0.001). Additionally, 3D-micro MR images and angiography of mice of high quality and detail were obtained using PAMAM-(1B4M-Gd)x as a macro-molecular MRI contrast agent with a 1.5-T clinical MRI instrument. Numerous fine vessels of approximately 200 microm diameter were visualized on subtracted 3D-MR angiographms with G6D-(1B4M-Gd)(192). The quality of the images was sufficient to estimate the microvasculature of cancerous tissue for anti-angiogenesis therapy and to investigate knockout mice. Magn Reson Med 45:454-460, 2001.Magnetic Resonance in Medicine 04/2001; 45(3):454-60. · 2.96 Impact Factor -
Article: FDG-PET of autoimmune-related pancreatitis: preliminary results.
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ABSTRACT: 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.European Journal of Nuclear Medicine 01/2001; 27(12):1835-8. -
Article: Delayed (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas.
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ABSTRACT: Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) has been used for the evaluation of various tumors, but accumulation in inflammatory lesions makes it a controversial modality. The aim of this study was to investigate the usefulness of delayed scanning in differentiation between malignant and benign lesions in the pancreas. Forty-seven patients with suspected pancreatic carcinoma were studied by FDG-PET. All patients received approximately 370 megabequerels of FDG after a transmission scan, and an emission scan was performed 1 hour and 2 hours later for all patients. A subset of 19 patients was also scanned at 3 hours postinjection. The standardized uptake value (SUV) was determined, and the retention index was calculated by dividing the increase in the SUV between 1 hour and 2 hours postinjection by the SUV at 1 hour postinjection. Of 27 malignant lesions, the SUVs of 22 lesions increased at 2 hours postinjection, whereas the FDG uptake in 17 of 20 benign lesions decreased. The SUVs at 3 hours postinjection were higher than those at 2 hours postinjection in 9 of 14 malignant lesions and in 2 of 5 benign lesions. Malignant lesions showed a higher retention index than benign lesions (mean +/- standard deviation: 12. 36 +/- 13.37 and -7.05 +/- 17.28, respectively; P < 0.0001). Applying an SUV of 2.5 at 1 hour postinjection with the cut-off value for the differentiation between malignant and benign lesions caused one false negative result and seven false positive results, with a diagnostic accuracy of 83.0% (39 of 47 patients). However, combining the retention index with the SUV obtained at 2 hours postinjection provided a higher diagnostic accuracy (91.5%; 43 or 47 patients) than the SUV alone. The false negative rate remained constant when the retention index was taken into account. Images at 3 hours postinjection usually were unhelpful in differentiating further between malignant lesions and benign lesions. The current data suggest that delayed FDG-PET scanning at 2 hours postinjection may contribute to differentiation between malignant and benign lesions in the pancreas.Cancer 12/2000; 89(12):2547-54. · 4.77 Impact Factor -
Article: Establishment and characterization of a breast cancer cell line expressing Na+/I- symporters for radioiodide concentrator gene therapy.
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ABSTRACT: 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. 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. 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. 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.Journal of Nuclear Medicine 11/2000; 41(11):1898-904. · 6.38 Impact Factor -
Article: Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.
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ABSTRACT: 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.European Journal of Nuclear Medicine 10/2000; 27(9):1334-9. -
Article: Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice.
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ABSTRACT: Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated (131)I-labeled anti-CEA monoclonal antibody (MAb) (24 - 38 microg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72 - 115 microg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P < 0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P < 0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD.Japanese journal of cancer research: Gann 06/2000; 91(6):622-8. -
Article: Evaluation of pancreatic islet cell tumors by fluorine-18 fluorodeoxyglucose positron emission tomography: comparison with other modalities.
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ABSTRACT: Pancreatic islet cell tumors are potentially malignant tumors and are often difficult to detect with current imaging modalities. Positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose (FDG) is an imaging technique with high sensitivity for malignant tumors. The aim of this study was to assess the feasibility of FDG PET to detect pancreatic islet cell tumors. Nineteen lesions of histologically proved islet cell tumors were evaluated in 12 patients (5 men, 7 women; ages 22 to 77 years). FDG uptake was analyzed semiquantitatively as a standardized uptake value. The diagnostic accuracy of PET was compared with that of US, CT, and MRI. Of 19 lesions, 8 showed positive PET results (standardized uptake value > 2.3), and localization was indicated in 2 lesions. In nine tumors that were not detected by PET, seven were small tumors ranging from 1.5 to 8 mm in diameter and were not identified by other imaging methods. The sensitivity rate of PET was 53%, whereas those of US, CT, and MRI were 53%, 50%, and 53%, respectively. Our data suggest that FDG PET has a limitation in that it does not detect some small-sized islet cell tumors, mainly depending on their size, but it has potential utility as a complementary modality for other imaging techniques.Clinical Nuclear Medicine 02/2000; 25(2):115-9. · 3.67 Impact Factor -
Article: Asialoglycoprotein receptor scintigraphy in evaluation of auxiliary partial orthotopic liver transplantation.
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ABSTRACT: The purpose of this study was to evaluate asialoglycoprotein receptor scintigraphy in the post-transplant monitoring of liver graft and native liver functions in recipients of auxiliary partial orthotopic liver transplantation (APOLT) from living donors. We performed 36 asialoglycoprotein receptor scintigraphies on 13 patients who had undergone APOLT for noncirrhotic metabolic liver diseases or for small-for-size grafts. The portal vein of the native liver was separated in 12 patients. Anterior dynamic images including the heart and both livers were obtained for 16 min after intravenous injection of 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA), and thereafter static SPECT images of both livers were obtained. Uptake rates from the blood to the graft and to the native liver were determined separately by Patlak plot graphical analysis. Relative uptake of GSA by the graft was calculated from transverse SPECT images. The relative volume of the graft liver was determined by CT. The relative uptake of GSA by the graft was higher or increased more rapidly than the relative volume of the graft in 8 of 11 patients with no severe complications concerning the graft. The relative uptake by severely damaged graft liver in 2 patients was much lower than the relative volume. The uptake rate of GSA by the graft was low in these 2 patients. The uptake rate by the native liver decreased when the portal vein was separated. The relative uptake of GSA was a better indicator of graft liver function than was anatomic volume. The uptake rate provided additional independent information of each liver. Asialoglycoprotein receptor scintigraphy is useful for distinguishing and monitoring the graft and native liver functions in patients who had undergone APOLT.Journal of Nuclear Medicine 10/1999; 40(9):1463-7. · 6.38 Impact Factor -
Article: Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET.
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ABSTRACT: This investigation was undertaken to evaluate 18F-labeled fluorodeoxyglucose (FDG) PET in monitoring patients after intraoperative radiotherapy (IORT) for unresectable pancreatic cancer and to compare its usefulness with CT. FDG PET was performed in 12 consecutive unresectable ductal adenocarcinoma patients before (n = 12) and after IORT (0.7-11.9 mo, n = 14). In the follow-up period, FDG PET results after IORT were divided into three groups: early (0-2.0 mo after IORT, n = 7), intermediate (2.1-4.0 mo, n = 5) and delayed period (4.1 mo or later, n = 2). FDG uptake at 60 min after injection of 185 MBq FDG under fasting conditions was analyzed with standardized uptake value (SUV). Three parameters, the highest SUV in the tumor, the area of tumor showing SUV of more than 2.0 and the average SUV in the tumor area were calculated. Ratios of each parameter after IORT to that before IORT were defined as residual uptake ratio (RUR)-1, -2 and -3, respectively. Tumor regression after IORT was evaluated with CT as tumor size ratio (TSR) every 2 mo. Results of RUR-1 and -3 were consistent with tumor size measured by CT. They decreased in 10 patients with partial response and increased in 2 patients with no change, although these 2 patients had abscesses. RUR-3 decreased consistently as 0.65+/-0.33 in 2 mo, 0.51+/-0.39 in 4 mo and 0.24 in 4 mo or later after IORT, respectively. RUR-1 decreased in early period, but demonstrated no change through the remaining periods. There were discrepancies between the results of RUR-2 and those of the other RURs. CT results revealed a slow decrease in tumor size, because TSR was 0.91 +/-0.10, 0.76+/-0.11 and 0.70+/-0.18 in 2, 4 and 6 mo after IORT, respectively. RUR-3 was smaller than TSR at 2 mo (P < 0.05) and 4 mo (P = 0.056). These results indicate that the measurement of the average SUV in the tumor area with FDG PET could evaluate the local response of pancreatic cancer after IORT earlier and more markedly than with CT. FDG PET was useful in monitoring patients after IORT, because the decrease of metabolism in pancreatic tumor could be detected earlier than the decrease in tumor size.Journal of Nuclear Medicine 10/1999; 40(9):1424-33. · 6.38 Impact Factor -
Article: Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody.
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ABSTRACT: The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.European Journal of Cancer 08/1999; 35(8):1281-5. · 5.54 Impact Factor -
Article: Contribution of PET in the detection of liver metastases from pancreatic tumours.
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ABSTRACT: Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the liver is basically high, metastatic liver tumours are known to be positive on positron emission tomography (PET). The purpose of this study is to evaluate the diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic cancer. Thirty-four patients with histologically proven malignant tumours of the pancreas underwent FDG-PET, computed tomography (CT) and transabdominal ultrasound (US). The findings of PET, CT and US were compared with the histopathologic findings at surgery or with clinical follow-up and the diagnostic accuracy of PET was evaluated. PET showed 28 regions of high FDG uptake (SUV = 3.3-9.1) in 13 patients. Twenty-six foci were metastatic lesions confirmed by surgery (n = 11), clinical follow-up (n = 10) or autopsy (n = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when the diagnosis by US or CT was unreliable because of the small size of the lesion. In two patients who had areas of high uptake in the liver, no metastases were detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients. Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a liver metastasis was found at surgery in one patient. The diagnostic accuracy of FDG-PET was 90%, which was comparable with that of US or CT. Our data suggest that PET is reliable in detecting liver, metastases from pancreatic cancer.Clinical Radiology 05/1999; 54(4):248-52. · 1.95 Impact Factor -
Article: A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment.
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ABSTRACT: Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.British Journal of Cancer 05/1999; 79(11-12):1794-9. · 5.04 Impact Factor -
Article: Radioimmunotherapy for liver micrometastases in mice: pharmacokinetics, dose estimation, and long-term effect.
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ABSTRACT: The pharmacokinetics of a therapeutic dose of 131I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/ 40 microg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 microm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0 % injected dose (ID)/g on day 1 to 17.8 %ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-microm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions.Japanese journal of cancer research: Gann 04/1999; 90(3):342-8. -
Article: Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.
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ABSTRACT: The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.Journal of Nuclear Medicine 04/1999; 40(4):685-92. · 6.38 Impact Factor
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Institutions
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1996–2001
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Kyoto University
- Department of Diagnostic Imaging and Nuclear Medicine
Kyoto, Kyoto-fu, Japan
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1999
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Miyazaki Prefectural Wood Utilization Research Center
Miyazaki-shi, Miyazaki-ken, Japan
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