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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 145 records · Page 8Linked to original sources

Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67.

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.

Animals↗

No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by [11C]propyl ketene method.

This article describes the preparation of sn-1,2-[11C]diacylglycerols and sn-1,3-[11C]diacylglycerols by a no-carrier-added reaction based on a labeling method using [1-11C]propyl ketene, which is one of the most potent acylating agents. [1-11C]Propyl ketene was produced by pyrolytic decomposition of [1-11C]butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine. We adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-[1-11C]butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-[11C]Diacylglycerol was also synthesized by [1-11C]propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-[11C]diacylglycerol were higher than those of sn-1,3-[11C]diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2-[11C]diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover.

Acylation↗

Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanomas.

The relationship between 3,4-dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) uptake and melanogenesis was studied using mice bearing two B16 melanomas: B16-F1 has a higher melanin synthesis ability and a slower growing rate than the higher metastatic B16-F10. A significantly higher 2-[18F]FDOPA uptake by B16-F1 than by B16-F10 and a reverse relationship for the uptake of [14C] 2-deoxy-2-fluoro-D-glucose and [3H]thymidine were observed 1 hr postinjection. F1-to-F10 ratios of both the 2-[18F]FDOPA uptake and the acid-insoluble radioactivity increased to about 5 at 6 hr, which paralleled the melanin content. FM3A mammary carcinoma showed a 2-[18F]FDOPA uptake similar to the B16-F10 but without the acid-insoluble radioactivity. With D,L-DOPA loading, a 55% decreased uptake by FM3A 1 hr postinjection was significantly greater than the 20% reduction in both melanomas. O-Methylated 2-[18F]FDOPA was a predominant acid-soluble metabolite in all tumors. Whole-body autoradiography discriminated the two melanomas clearly. 2-[18F]FDOPA may be a promising tracer for the selective imaging of melanogenesis.

Animals↗

Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography.

This is the first study of micro-autoradiography (micro-ARG) for [18F]2-fluoro-2-deoxy-D-glucose [( 18F]FDG). The localization of [18F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18F radioactivities in the specimen. The micro-ARG using positron emitting 18F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3H- or 14C-labeled tracers.

Animals↗

Visualization of histamine H1 receptors in dog brain by positron emission tomography.

Histamine H1 receptors were visualized in the living dog brain using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The regional distribution of these carbon-11 labeled compounds in the brain corresponded well with that of the histamine H1 receptors separately determined by in vitro binding assay. The radioactivity in the brain was reduced by treatment with triprolidine (1 mg/kg), a histamine H1 antagonist. The results of our study indicate that it is feasible to visualize histamine H1 receptors in human brain using these 11C-labeled compounds and PET.

Animals↗

The accumulation of 11C-methionine in cerebral glioma patients studied with PET.

Fourteen patients with cerebral gliomas were studied with positron emission tomography (PET) using L-[methyl-11C]methionine (11C-MET). Positive images of tumour were obtained in all cases regardless of histological grades. The analysis of differential absorption ratio (DAR) showed the higher accumulation of 11C-MET in high grade gliomas than in low grade gliomas. PET study with 11C-MET will be of great value not only in delineating the location of gliomas, but also in making a qualitative diagnosis from the view point of the biological properties of gliomas.

Adult↗

Clinical assessment of therapeutic effects on cancer using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography: preliminary study of lung cancer.

Using positron emission tomography, we studied the tumor uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG) in five lung cancer patients before and after anti-cancer therapy (radiotherapy and/or chemotherapy). The tumor uptake of 18FDG was classified as positive and negative; the former, by increasing the uptake of 18FDG with time, and the latter, by decreasing or the constant uptake of 18FDG. Before therapy, all cases tested positive. After therapy, three cases were negative and two cases remained positive. All negative cases corresponded to complete second 18FDG study. Our findings in the 18FDG study correlate with the clinical results. 18FDG is a promising method for assessing therapeutic effects on cancer clinically.

Adult↗

Synthesis of omega-[18F]fluoroalkyl analogs of YM-09151-2 for the measurement of D2-dopamine receptors with PET.

Two [18F]fluoroalkyl analogs of a neuroleptic YM-09151-2 were synthesized via nucleophilic [18F]fluorination of methanesulfonyloxy- or p-toluenesulfonyloxyalkyl derivatives using no-carrier-added [18F]fluoride. Although 3-[18F]fluoropropylaminobenzamide was obtained in good yield, the yield of 2-[18F]fluoroethyl derivative was severalfold lower. The product, N-[(2RS,3RS)-1-benzyl-2-methylpyrrolidin-3-yl]-5- chloro-2-methoxy-4-(3-[18F]fluoropropyl)-aminobenzamide, was shown to have a striatum-to-cerebellum ratio comparable to that of 11C labeled YM-09151-2 and thus to be a good candidate for measuring D2-receptors in vivo.

Animals↗

Tumor uptake of [48V]vanadyl-chlorine e6Na as a tumor-imaging agent in tumor-bearing mice.

[48V]Vanadyl-chlorine e6Na (48V-Chl) which was synthesized by insertion of 48V (positron emitter) into chlorine e6Na (Chl), a chlorophyll derivative having a similar structure to pheophorbide-a (Pheo), localized rapidly in experimental mammary carcinoma. The tumor-to-organ ratios of 48V-Chl were higher than those of 48V-labeled Pheo (48V-Pheo), and 48V-Chl showed a clear tumor image with low accumulation in liver, depending on the biodistribution of metal-free Chl having an affinity with tumor. 48V-Chl seems to be more suitable than 48V-Pheo as a tumor-imaging agent for photodynamic therapy of tumors.

Animals↗

Tumor uptake study of 18F-labeled N-acetylneuraminic acids.

In order to develop positron-emitting tracers for imaging metabolic functions of tumors with positron emission tomography, tumor uptake of N-acetyl-3-[18F]fluoroneuraminic acid and N-acetyl-2-deoxy-2,3-di-[18F]fluoroneuraminic acid was investigated in mice or rats. The two tracers showed similar tissue distribution patterns. After i.v. injection of each tracer into mice with an FM3A tumor, the radioactivity was very rapidly cleared from normal and tumor tissues. Only tumor-to-brain and tumor-to-muscle uptake ratios were greater than 1.0 for 2 h. In 7 types of tumor models, no selective tumor uptake of tracers was observed 30 min after injection. The metabolic alteration rate of N-acetyl-3-[18F]fluoroneuraminic acid in FM3A, liver and kidney was very slow. Neither tracer may be suitable for tumor imaging in vivo.

Animals↗

Specific binding of [3H]pyrilamine to histamine H1 receptors in guinea pig brain in vivo: determination of binding parameters by a kinetic four-compartment model.

The binding of [3H]pyrilamine, a selective ligand of histamine H1 receptors, to guinea pig brain in vivo was compared with its binding to a brain homogenate. The pharmacological properties (regional distribution, saturability, and stereoselectivity) of the [3H]pyrilamine binding in vivo were similar to those of the in vitro binding to brain homogenate. A dynamic four-compartment model was proposed for the analysis of the kinetics of [3H]pyrilamine binding in vivo. The receptor constants in vivo were determined by a computer-fitting method after correcting the radioactivity of arterial plasma and brain for the presence of radioactive metabolites. The in vivo association and dissociation were 213 and 42 times, respectively, slower than those of in vitro binding at 37 degrees C. A possible mechanism for slow association and dissociation in vivo is discussed.

Aminopyridines↗

Stability of cerebral blood flow and oxygen metabolism during normal aging.

Cerebral blood flow and oxygen metabolism in aged normal subjects were measured with positron emission tomography and their relationship with brain atrophy was evaluated. Brain atrophy progressed in a linear fashion during aging while cerebral blood flow and oxygen metabolism were well preserved. The finding suggests that brain atrophy is an aging process less dependent on cerebral blood flow and metabolism over the course of normal aging.

Aged↗

Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study.

To investigate the effects of long-term pressure overload on regional myocardial substrate use, we performed quantitative autoradiography using 2-deoxy-D-[U-14C]glucose (14C-DG) and beta-methyl[1-14C]heptadecanoic acid (14C-BMHDA) in conscious rats with a 10-week ascending aortic constriction. Heart weight/body weight ratio increased by 27% in aortic-constricted rats as compared with sham-operated rats (p less than 0.01). Myocardial 14C-DG uptake increased (258 +/- 63 vs. 144 +/- 41 nCi/g, p less than 0.01, n = 6 for each group); however, 14C-BMHDA extraction decreased (251 +/- 69 vs. 342 +/- 75 nCi/g, p less than 0.05, n = 7 for each group) in aortic-constricted rats as compared with sham-operated rats. In sham-operated rats, both 14C-DG and 14C-BMHDA uptakes were higher in the left ventricular anterior and lateral walls as compared with the posterior wall or the interventricular septum. In aortic-constricted rats, 14C-DG uptake also increased in the interventricular septum, as well as in the left ventricular anterior and lateral walls, as compared with the posterior wall. There was, however, no regional difference in 14C-BMHDA extraction among these four regions. Myocardial blood flow distribution determined by 4-[N-methyl-14C]iodoantipyrine or myocyte width showed no regional variations among the four regions, either in aortic-constricted or sham-operated rats. Regional interstitial fibrosis was small in either group. The present study suggests that myocardial substrate uptake is altered nonhomogeneously, and that the nonhomogeneity is not because of regional variations in blood flow distribution, myocyte hypertrophy, or interstitial fibrosis. The results of angiotensin II-induced acute pressure overloading in other sham-operated rats, in which a remarkable increase in myocardial 14C-BMHDA extraction (n = 3, p less than 0.01) and no difference in 14C-DG uptake (n = 3) as compared with normotensive sham-operated rats were elicited, suggest that the findings in aortic-constricted rats are not direct responses to increased left ventricular pressure itself but rather should be explained by still unknown factors related to prolonged pressure overload.

Acute Disease↗

Reduced regional cerebral metabolic rate for glucose at the terminal stage in a case of late infantile neuronal ceroid lipofuscinosis.

Regional cerebral metabolic rate for glucose was determined for six different areas of the gray matter in an 8-year-old girl with late infantile neuronal ceroid lipofuscinosis. In all regions, the rates were almost half of the control values. The regional cerebral metabolic rate for glucose was relatively preserved in the striatal region and severely reduced in the frontal cortex.

Blood Glucose↗

Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography.

Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.

Aged↗

18F-fluoro-2'-deoxyuridine as a tracer of nucleic acid metabolism in brain tumors.

The value of 18F-fluoro-2'-deoxyuridine (18F-FUdR) as a tracer for nucleic acid metabolism was studied using an experimental rat brain-tumor model. The 18F activity in the tumor tissue 45 minutes after intravenous injection of 18F-FUdR was about 12 times higher than that in the contralateral cortex. Double-labeled autoradiography with 18F-FUdR and 14C-thymidine revealed similar brain-tumor images. In contrast, an autoradiographic comparison of 18F-FUdR with 14C-aminoisobutyric acid, which reveals the impairment of the blood-brain barrier, showed very different images. Also, the 18F radioactivity in the tumor tissue was at a constant level for 30 to 120 minutes, whereas a notable increase in 18F activity with time was observed in nucleotides and acid-insoluble fractions. These results suggest that the distribution pattern of 18F-FUdR closely correlates with the metabolism of nucleic acid and that this drug could be a useful tracer for positron emission tomography.

Animals↗

Differential diagnosis of lung tumor with positron emission tomography: a prospective study.

To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.

Adult↗