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Eriko Tsukamoto

Publications and source records attributed to Eriko Tsukamoto.

16 recordsLinked to original sources

Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V.

UNLABELLED: Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with (99m)Tc to detect apoptosis in vivo. To determine the effectiveness of imaging with this agent as a reflection of the degree of apoptosis after the first dose of chemotherapy, we studied rats with an engrafted hepatoma. METHODS: Annexin V was labeled with (99m)Tc (specific activity, 3.0 MBq/ micro g protein). Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the left calf muscle, the rats were randomized to receive a single dose of cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. (99m)Tc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-iodoanitpyrine was determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested at necropsy was performed to detect apoptosis in the tumor. RESULTS: Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue after normalization to the animal's weight [%ID/g/kg]) of (99m)Tc-annexin V (0.070 +/- 0.007 %ID/g/kg for treated rats and 0.046 +/- 0.009 %ID/g/kg for controls, P < 0.001). (14)C-iodoantipyrine uptake was similar in the treated and untreated groups. The number of TUNEL-positive cells in the tumor was significantly larger in the treated rats (297.70 +/- 50.34 cells/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001). CONCLUSION: Tumor uptake of (99m)Tc-annexin V was significantly increased by a single dose of cyclophosphamide treatment, and the increase was concordant with the number of TUNEL-positive cells in the tumor. The current results are suggestive of the utility of (99m)Tc-annexin V as a noninvasive means to assess tumor response, although further testing, including clinical evaluation, is required.

Animals↗

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

UNLABELLED: 1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.

Animals↗

Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer.

Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [(11)C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [(11)C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [(11)C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV(6-10 min) by the SUV(16-20min), were calculated to evaluate the accumulation of [(11)C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6+/-0.8) was significantly higher than that of the rectum (1.7+/-0.4) or bone marrow (1.3+/-0.3) ( P<0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4+/-0.7) was significantly higher than both the SUV for the normal prostate of subjects aged > or =50 years (2.3+/-0.7) and that of subjects with BPH (2.1+/-0.6) ( P<0.01 in each case). The primary prostate cancer in six cases was visualised by [(11)C]acetate PET. However, the difference in the SUV between subjects aged > or =50 with normal prostate or with BPH and the patients with prostate cancer (1.9+/-0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged > or =50 with normal prostate (0.98+/-0.04) or BPH (0.96+/-0.08) and patients with prostate cancer (1.02+/-0.12). In conclusion, a normal prostate exhibits age-related physiological accumulation of [(11)C]acetate. Careful interpretation of [(11)C]acetate PET images of prostate cancer is necessary because the SUV and the E/L ratio for the normal prostate and for BPH overlap significantly with those for prostate cancer.

Acetates↗

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas.

PURPOSE: Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS: The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS: Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION: This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

Adult↗

Clinical role of (18)F-FDG PET for initial staging of patients with extrahepatic bile duct cancer.

In extrahepatic bile duct cancer, preoperative evaluation is important because only surgical excision of all detectable tumours is associated with improvement in 5-year survival. However, morphological imaging techniques, including computed tomography (CT), are still insufficient for accurate staging. The purpose of this study was to assess the additional value, in relation to CT, of 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography ((18)F-FDG PET) for the evaluation of extrahepatic bile duct cancer. Thirty patients with extrahepatic bile duct cancer underwent both (18)F-FDG PET and CT for initial staging. The results of the two modalities for evaluation of primary tumours and regional lymph nodes were compared with the final diagnoses based on pathological or clinical findings. The primary tumours were interpreted as malignant on the basis of CT in 24 (80%) of the patients, while (18)F-FDG PET revealed increased (18)F-FDG uptake in 18 (60%) of them. On the other hand, (18)F-FDG PET showed focal accumulation of (18)F-FDG in the bile duct in three of the six patients with equivocal findings on CT. The sensitivity, specificity and accuracy of CT for regional lymph node metastases were 54%, 59% and 57%, while those of (18)F-FDG PET were 38%, 100% and 73%, respectively. The specificity of (18)F-FDG PET for regional lymph node metastases was significantly higher than that of CT ( P<0.01). Of 14 patients with N1 or N2 disease diagnosed by CT, only seven (50%) had a final diagnosis of regional lymph node metastasis. In these 14 patients, (18)F-FDG PET accurately evaluated the N component of the disease in 12 patients (86%). In conclusion, in the initial staging of patients with extrahepatic bile duct cancer, (18)F-FDG PET offers additional value in relation to CT in evaluating both the primary tumour and regional lymph nodes.

Adenocarcinoma↗

Decreased endothelium-dependent coronary vasomotion in healthy young smokers.

Chronic cigarette smoking alters coronary vascular endothelial response. To determine whether altered response also occurs in young individuals without manifest coronary disease we quantified coronary blood flow at rest, following adenosine vasodilator stress and during the cold pressor test in healthy young smokers. Myocardial blood flow (MBF) was quantified by oxygen-15 labelled water positron emission tomography in 30 healthy men aged from 20 to 35 years (18 smokers and 12 non-smokers, aged 27.4 +/- 4.4 vs 26.3 +/- 3.3). The smokers had been smoking cigarettes for 9.4 +/- 4.9 pack-years. MBF was measured at rest, during intravenous adenosine triphosphate (ATP: 0.16 mg kg(-1) min(-1)) infusion (hyperaemic response), and during cold pressor test (CPT) (endothelial vasodilator response). Rest MBF and hyperaemic MBF did not differ significantly between the smokers and the non-smokers (rest: 0.86 +/- 0.11 vs 0.92 +/- 0.14 and ATP: 3.20 +/- 1.12 vs 3.69 +/- 0.76 ml g(-1) min(-1); P = NS). Coronary flow reserve was similar between the two groups (smokers: 3.78 +/- 1.83; non-smokers: 4.03 +/- 0.68; P = NS). Although CPT induced a similar increase in rate-pressure product (RPP) in the smokers and the non-smokers (10,430 +/- 1,820 vs 9,236 +/- 1,356 beats min(-1) mmHg(-1)), CPT MBF corrected by RPP was significantly decreased in the smokers (0.65 +/- 0.12 ml g(-1) min(-1)) compared with the non-smokers (0.87 +/- 0.12 ml g(-1) min(-1)) ( P < 0.05). In addition, the ratio of CPT MBF to resting MBF was inversely correlated with pack-years ( r = -0.57, P = 0.014). Endothelium-dependent coronary artery vasodilator function is impaired in apparently healthy young smokers.

Adenosine Triphosphate↗

Accuracy of plasma sample methods for determination of glomerular filtration rate with 99mTc-DTPA.

UNLABELLED: The plasma sample method following a single injection of radioactive markers has been proved to be simple and accurate for the determination of glomerular filtration rate (GFR) in clinical practice. The aim of this study was to assess clinical accuracy of single-, two- and multi-sample methods. METHODS: The study was performed on 50 patients with various degrees of renal dysfunction (29 males and 21 females; aged 27 to 90 years). As a reference the true GFR (GFRt) was determined by means of the two-compartment model curve fitting 10 plasma samples following a single-injection of 99mTc-DTPA. The GFRt was compared to the GFR estimated by the Christensen and Groth's single-sample (GFRcg), two-sample (GFR2s) and multi-sample (GFRm) between 75 and 300 min after the injection. The GFRs by two- and multi-sample methods were determined with the slope and intercept algorithm and its overestimation was corrected by Brochner-Mortensen's formula. RESULTS: In 49 patients with GFR between 12 and 169 ml/min/1.73 m2, the standard deviation of difference (95% limits of agreement) between GFRt and GFRcg at 180 min was 6.513 ml/min/l73 m2 (-16.5 approximately 9.5 ml/min/1.73 m2), which was somewhat closer than 7.311 ml/min/1.73 m2 (-12.5 approximately 16.5 ml/min/1.73 m2) in GFR2s in slow clearance phase at 120 min and 240 min. However, the single-sample method tended to show some scattering in GFR below 30 and above 140 ml/min/ 1.73 m2. On the contrary, the 2-sample method tended to be scattered in GFR above 120 ml/min/ 1.73 m2. CONCLUSION: In view of its accuracy and technical simplicity, the single-sample method is first choice in a routine practice. The two-sample method is essential of choice for a patient in whom the GFR is expected to be below 30 ml/min/1.73 mi2. These two methods may be chosen selectively in dependence on the preserved renal function which is expected at time of the test.

Adult↗

The effect of scatter correction on 123I-IMP brain perfusion SPET with the triple energy window method in normal subjects using SPM analysis.

Scatter correction (SC) using the triple energy window method (TEW) has recently been applied for brain perfusion single-photon emission tomography (SPET). The aim of this study was to investigate the effect of scatter correction using TEW on N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPET in normal subjects. The study population consisted of 15 right-handed normal subjects. SPET data were acquired from 20 min to 40 min after the injection of 167 MBq of IMP, using a triple-head gamma camera. Images were reconstructed with and without SC. 3D T1-weighted magnetic resonance (MR) images were also obtained with a 1.5-Tesla scanner. First, IMP images with and without SC were co-registered to the 3D MRI. Second, the two co-registered IMP images were normalised using SPM96. A t statistic image for the contrast condition effect was constructed. We investigated areas using a voxel-level threshold of 0.001, with a corrected threshold of 0.05. Compared with results obtained without SC, the IMP distribution with SC was significantly decreased in the peripheral areas of the cerebellum, the cortex and the ventricle, and also in the lateral occipital cortex and the base of the temporal lobe. On the other hand, the IMP distribution with SC was significantly increased in the anterior and posterior cingulate cortex, the insular cortex and the medial part of the thalamus. It is concluded that differences in the IMP distribution with and without SC exist not only in the peripheral areas of the cerebellum, the cortex and the ventricle but also in the occipital lobe, the base of the temporal lobe, the insular cortex, the medial part of the thalamus, and the anterior and posterior cingulate cortex. This needs to be recognised for adequate interpretation of IMP brain perfusion SPET after scatter correction.

Adult↗

Increased [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) yield with recycled target [18O]water: factors affecting the [18F]FDG yield.

The reuse of [18O] water after being purified by distillation has been reported to give lower [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) yields, probably due to the presence of organic impurities. In our routine production of [18F]FDG, however, we observed increased [18F]FDG yields with recycled [18O]water. Thus, factors affecting [18F]FDG yield were examined using as-purchased (virgin) and recycled (by photochemical combustion and distillation) [18O]water. [18F]FDG was synthesized by nucleophilic 18F-fluorination on a quaternary 4-aminopyridinium resin. The recycled [18O]water gave an [18F]FDG yield significantly higher than did the virgin water, without any significant difference in the [18F]fluoride yield. Levels of several ionic impurities including Cl- and Ca2+ were significantly higher in the virgin [18O]water than in the recycled water, while significantly larger amounts of organic impurities were detected in the former. Hence, trace amounts of organic impurities were not responsible for the lower [18F]FDG yield. Chloride anion in the [18O]water may compete with [18F]fluoride to lower the [18F]FDG yield.

Journal Article↗

Chemical impurities in [18F]FDG preparations produced by solid-phase 18F-fluorination.

[18F]FDG was produced by solid-phase 18F-fluorination (resin method) and chemical impurities were determined in the [18F]FDG preparations by ion chromatography. The major chemical impurities were D-glucose (90.5 +/- 6.4 microg/mL), 2-chloro-2-deoxy-D-glucose (11.8 +/- 2.7 microg/mL), and D-mannose (1.7 +/- 0.7 microg/mL), which were expected to be present by considering the synthetic routes. An FDG mass (0.5 +/- 0.2 microg/mL) was also detected in the preparations. No notable radiochemical impurities, including 2-[18F]fluoro-2-deoxy-D-mannose, were detected in the [18F]FDG preparations. Thus, the levels of several chemical impurities were determined in the [18F]FDG preparations produced by solid-phase 18F-fluorination.

Chromatography, Ion Exchange↗

In vitro uptake of [1-14C]Octanoate in brain slices of rats: basic studies for assessing [1-11C]Octanoate as a PET tracer of glial functions.

To clarify the contribution of glial cells to octanoate uptake into the brain, we determined the effects of fluoroacetate, a selective inhibitor of glial metabolism, on in vitro brain uptake of [1-14C]octanoate, using rat brain slices. The [1-14C]octanoate uptake significantly decreased, depending on the concentration of fluoroacetate (p = 0.001). The [1-14C]octanoate uptakes at 5 mM (0.23 +/- 0.05% uptake/mg slice) and 25 mM fluoroacetate (0.12 +/- 0.01% uptake/mg slice) were significantly lower than that at control (0.29 +/- 0.02% uptake/mg slice, p < 0.05 and p < 0.001, respectively). The results demonstrate the contribution of glial cells to octanoate uptake into the brain. The potential of [1-11C]octanoate as a PET tracer for studying glial functions is suggested.

Animals↗

A simplified and improved synthesis of [11C]phosgene with iron and iron (III) oxide.

[11C]Phosgene ([11C]COCl2), a useful precursor for labeling several radiopharmaceuticals, is generally produced by catalytic oxidation of [11C]carbon tetrachloride over Fe granules, although in low yields or with poor reproducibility. In order to develop am improved synthesis of [11C]phosgene, two oxidizing agents, Fe2O3 and CuO, were examined. The yield of [11C]phosgene was significantly increased using Fe2O3 powder mixed with Fe granules, while the use of CuO alone, or CuO powder mixed with Fe granules resulted in an insignificant yield. The yield and specific activity of S- (-) [11C]CGP-12177 synthesized using Fe2O3 powder mixed with Fe granules were markedly higher than those synthesized by the previous methods using Fe granules alone or Fe granules mixed with Fe powder. Thus, in the present study, we developed a simple and practical method for the synthesis of [11C]phosgene, which provided an improved yield of S- (-) [11C]CGP-12177.

Carbanilides↗

Lung tumors evaluated with FDG-PET and dynamic CT: the relationship between vascular density and glucose metabolism.

PURPOSE: The aim of the current study was to evaluate the relationship between FDG-PET and dynamic CT in lung tumors. METHOD: Forty consecutive patients with pulmonary tumors underwent whole-body FDG-PET and contrast-enhanced dynamic CT. The size of tumors was 2.6 +/- 0.2 cm (mean +/- SD) at the largest diameter. The standardized uptake value (SUV) of FDG-PET, peak attenuation (APA), and relative flow (RF) of dynamic CT were evaluated. All patients underwent surgery, and tissue samples were available to be studied. The intratumoral microvessel densities (MVDs) were counted and compared with the radiologic parameters. The duration between radiologic examinations and surgery was within 2 weeks in all patients. RESULTS: The mean SUV, APA, and RF of lung cancers were significantly higher than those of benign lesions (p < 0.05). The mean APA and RF of lung cancers correlated with mean SUV (APA : r = 0.665, p < 0.0001; RF: r = 0.848, p < 0.05) and mean MVD (APA: r = 0.801, p < 0.0001; RF: r = 0.723, p < 0.05). The mean SUV of lung cancers correlated with the mean MVD (r = 0.612, p < 0.001). No correlation was found between the mean APA, RF, SUV, and MVD in benign tumors. CONCLUSION: The APA and RF of dynamic CT correlated with the SUV of FDG-PET imaging in lung cancer. The APA and RF of dynamic CT as an index of blood pooling may be related to increased glucose metabolism in lung cancer.

Adult↗