Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 109 records · Page 6Linked to original sources

PubMed1992

Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model.

The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. The highest mean uptake by the five different tumors was found for [3H]Thd, followed in order by [18F]FDG, [11C]Met, 2-[18F]FdGal, [18F]FdUrd, 2-[18F]FdFuc and 6-[18F]FFuc. The tumor-to-tissue uptake ratios indicated that the nucleosides, [11C]Met and 6-[18F]FFuc were better tracers in the brain region. All the tracers except for the fucose analogs were suitable for the thoracic region, while [11C]Thd and [18F]FDG were superior in the abdominal region. In comparison with the primary tumor model of Lewis lung carcinoma (3LL), [3H]Thd uptake in the artificial metastatic 3LL model showed the maximum enhancement, followed by [18F]FDG, [11C]Met and the other tracers. The [18F]FDG uptake correlated with the [3H]Thd uptake. [18F]FdUrd, 6-[18F]FFuc and 2-[18F]FdGal could be used for distinguishing different types of tumors. The combined use of these radiotracers can possibly allow the assessment of tumor metabolism, and this indicates the viability of tumors.

Animals↗

PubMed1992

4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET.

The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L-[14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging.

Animals↗

PubMed1992

Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D-glucosamine.

In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D-glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P less than 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low metastatic potential). Analysis of metabolites showed that acid-insoluble fraction was the largest one in the liver by 60 min, whereas in the tumors, phosphates fraction was the major metabolite. Slower metabolism in tumors was suggested, and it may be one of the reasons for the difficulty of detecting the characteristics of their hyaluronic acid synthesis. 18F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C]glucose and [6-3H]thymidine failed to demonstrate any difference between tumors' metastatic variants in vivo.

Acetylglucosamine↗

PubMed1992

Dose-responsive effect of radiotherapy on the tumor uptake of L-[methyl-11C]methionine; feasibility for monitoring recurrence of tumor.

The L-[methyl-11C]methionine [( 11C]Met) uptake by rat AH109A tumor was decreased irradiation-dose dependently from the control to 5, 10 and 20 Gy. After 10 Gy irradiation, the [11C]Met uptake decreased earlier than the tumor volume reduction, and later, it significantly increased earlier than the recurrent growth. Double tracer autoradiography with [14C]Met and 4-[18F]fluoroantipyrine showed a decrease in the [14C]Met tumor uptake without change of blood flow after irradiation. The [11C]Met uptake representing amino acid metabolism is a sensitive indicator for monitoring radiotherapeutic effect on tumor.

Animals↗

PubMed1992

Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil.

PURPOSE: The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea. METHODS: Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU. RESULTS: Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing. CONCLUSION: These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.

Animals↗

PubMed1992

Active melanogenesis in non-S phase melanocytes in B16 melanomas in vivo investigated by double-tracer microautoradiography with 18F-fluorodopa and 3H-thymidine.

3,4-Dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) and [6-3H]thymidine ([3H]Thd) were simultaneously injected into mice transplanted with B16 melanomas of FM3A mammary carcinoma. Melanogenesis was differentiated from DNA synthesis in the mitotic cell cycle by monitoring grain distribution with double-tracer microautoradiography. The percentages of pigmented cells were inversely proportional to those of [3H]Thd-labelled cells, indicating that the greater the number of melanocytes, the smaller was the number of proliferating cells. The number of grains produced by 2-[18F]FDOPA in the [3H]Thd-unlabelled melanocytes was significantly higher (P < 0.001) than the numbers in the [3H]Thd-labelled melanocytes and in nonmelanocytes. The [3H]Thd-unlabelled non-melanocytes and FM3A cells showed the lowest accumulation of 2-[18F]DOPA, which may have resulted from the basic amino acid demand by malignant neoplasms via amino acid transport. The [3H]Thd-labelled cells, regardless of whether they were pigmented or not, had slightly more grains with 2-[18F]FDOPA than the [3H]Thd-unlabelled non-melanocytes (P < 0.05), which may have resulted from the enhanced amino acid requirement for proliferation. Melanogenesis appeared to be activated only in the non-S phase of the mitotic cycle in melanocytes.

Animals↗

PubMed1992

Age-dependent decrease in histamine H1 receptor in human brains revealed by PET.

Age-related changes in histamine H1 receptors were studied using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The frontal, parietal and temporal cortices showed age-related decreases in binding of approximately 13% per decade. In contrast, the thalamus showed no apparent decrease in binding during normal ageing because of its higher nonspecific binding. Post mortem studies also indicated that the nonspecific binding of [3H]pyrilamine in the thalamus was approximately 112% higher than that in the cortex. However, no significant decrease in histamine H1 receptors with age was observed by in vitro binding assays of autopsied human frontal cortex. Possible reasons are given for the larger effects of age observed in the PET study than in the in vitro post mortem binding study.

Adolescent↗

PubMed1992

Receptor autoradiography with 11C and [3H]-labelled ligands visualized by imaging plates.

The distribution of histamine H1, H3, dopamine D1 and D2 receptors in the brain was studied by receptor autoradiography using a high-sensitivity and high-resolution imaging plate system. [3H]Pyrilamine, [3H](R)alpha-methyl-histamine, [11C]SCH23390, and [11C]N-methylspiperone (or [11C]YM-09151-2) were used as ligands to identify H1, H3, D1 and D2 receptors, respectively. Two different receptors (dopamine D2 and histamine H3) could be also labelled simultaneously in a single cryostat-sliced section using [11C]N-methylspiperone and [3H](R)alpha-methylhistamine, respectively. The imaging plate system is useful for receptor autoradiography of positron emitter-labelled and tritium-labelled receptor-ligands because of its high sensitivity.

Animals↗

PubMed1992

Differential diagnosis of idiopathic fibrosis from malignant lymphadenopathy with PET and F-18 fluorodeoxyglucose.

Idiopathic fibrosis and malignant lymphoma were studied with positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (F-18DG). Cases of retroperitoneal fibrosis and sclerosing peritonitis showed low F-18DG uptake with the mass/muscle radioactivity (M/M) ratio 2.0 and 1.9, respectively. A case of para-aortic adenopathy from malignant lymphoma showed high F-18DG uptake with the M/M ratio 9.4. F-18DG PET study may be useful for the differential diagnosis of idiopathic fibrosis and malignant lymphadenopathy.

Aged↗

PubMed1992

Positron emission tomography for treatment evaluation and recurrence detection compared with CT in long-term follow-up cases of lung cancer.

Two cases of lung cancer were studied with positron emission tomography (PET) using L-[methyl-C-11]methionine (C-11 Met) and CT scans five to six times during long-term follow-up after radiotherapy. In a large cell carcinoma with mediastinal invasion, C-11 Met tumor uptake showed a rapid decrease after radiotherapy, corresponding to clinical improvement, and detected recurrence at 11 months, as confirmed by biopsy. Tumor volume by CT showed no significant changes during this time. A squamous cell carcinoma of the superior sulcus (Pancoast type) showed rapid changes in C-11 Met tumor uptake and similar changes in tumor volume during two courses of radiotherapy and recurrence over a period of 25 months. PET evaluation of tumor viability seems to be valuable for treatment evaluation, and results match the tumor volume changes measured by CT.

Aged↗

PubMed1992

A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine.

A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L-phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L-[18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET.

Animals↗

PubMed1992

Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography.

We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11C]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.

Adult↗

PubMed1992

Efficiency of grain production and latent image fading in F-18 micro-autoradiography.

In 18F micro-autoradiography using a frozen section method, the grain production was measured relative to the exposure time and radioactivity. The grain production increased until 6-hr exposure, but 7-hr or longer exposure induced a characteristic of latent image fading. However, the ratios of the efficiency of grain production between two different 18F-radioactivities (11.9 and 2.3 mBq/100 microns2) were constant over experimental exposure times, thus indicating that quantitative analysis by grain counting is preserved.

Animals↗

PubMed1992

Tumor radiotherapy monitoring with radioscintigraphy tracers: a comparative study with multiple-tracer technique.

A comparative multiple-tracer study was performed to assess the tracer feasibility of monitoring tumor radiotherapy. Metabolic tracers for glucose, amino acid, nucleic acid metabolism: F-18-FDG, C-14-Met, H-3-Thd, and F-18-FdUrd and conventional Ga-67 were compared in the same AH109A radiotherapy model using a new quadruple-tracer technique. F-18-FDG showed a large uptake change and a steady response to radiotherapy which is similar to Ga-67. F-18-FdUrd showed a rapid decrease, but the range of change in uptake was narrow. H-3-Thd and C-14-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that if labeled with C-11, they may be feasible for PET study.

Animals↗

PubMed1992

Imaging of neurotransmitter receptors in the living human brain by positron emission tomography (PET).

More than 30 receptors or subtypes will be investigated in various neurological and psychiatric disorders using PET in the near future. However, the data obtained by PET should be carefully evaluated, because the PET method is based on the ligand-receptor binding in vivo. Extensive studies on animals and autopsied human brain samples are important to assess the significance of the findings revealed by PET technique to substantiate its validity.

Aging↗

PubMed1992

Membrane trapping of carbon-11-labeled 1,2-diacylglycerols as a basic concept for assessing phosphatidylinositol turnover in neurotransmission process.

The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because lipase predominantly hydrolyzes the 1- or 3-position of rac-1,2-[11C] DAG, which should be the main factor producing the differences in uptake values in other organs. Cholinergic stimulation prompted accumulation of 1,2-[11C]DAG in the conscious rat brain. In conclusion, sn-1,2-[11C]DAG, administered even in the racemic mixture, could serve as a tracer that becomes mixed with receptor-linked PI turnover and could accumulate in the brain based on the membrane trapping mechanism.

Animals↗

PubMed1992

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.

Animals↗

PubMed1992

[Autoradiographic demonstration of 18F-FDG distribution within mouse FM3A tumor tissue in vivo].

To demonstrate the distribution of 2-deoxy-2-18F-fluoro-D-glucose (FDG) within the tumor in vivo, C3H/He mice transplanted with FM3A tumors were studied one hour after intravenous injection of FDG using whole-body, macro- and micro-autoradiography. The whole-body autoradiograph showed that the tumor mass as well as the brain, heart, bone marrows, and the diaphragm and crus diaphragm were clearly visualized. The macro-autoradiograph showed the heterogeneous distribution of FDG in the tumor mass. Markedly dense areas surrounding the tumor and the necrotic area were observed. Micro-autoradiograph showed the high grain densities in the macrophages between the necrosis and viable tumor cells, and in the young granulation tissues demarcating between the tumor and surrounding intact host tissues. Our results showed that the FDG uptake in the tumors may reflect not only the uptake by the tumor cells but also that by the inflammatory reaction elements.

Animals↗