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BioMed Research International 2014There is little investigation for the functional roles of peripheral dopamine. [(18)F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic...
There is little investigation for the functional roles of peripheral dopamine. [(18)F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic tumors) and neuroimaging (i.e., Parkinson's disease and Huntington's disease). Here, we accessed side effects of recreational drugs such as ketamine, cocaine, and methamphetamine on dopamine neurons in peripheral organs by using positron emission tomography (PET) imaging and quantitative whole-body autoradiography (QWBAR) with [(18)F]FDOPA. The images were applied for the measurement of specific binding ratios (SBRs) of striatum with the cerebellum as the reference region. Clear striatal [(18)F]FDOPA-derived radioactivity was observed. Moderate level of radiotracer accumulation was presented in the mucosal layers of the stomach and small intestine. The medulla layers of kidney had higher radioactivity than that of the cortex. Blocking images markedly eliminated the specific binding of [(18)F]FDOPA in the striatum and in peripheral organs such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory effect on striatal [(18)F]FDOPA-derived radioactivity followed by cocaine and methamphetamine. The current results demonstrated a useful crossing-validating tool that enhances the capability of [(18)F]FDOPA for further investigations of the alteration of dopaminergic neurons in the brain disorder or cancer diseases in peripheral tissues.
Topics: Animals; Autoradiography; Cerebellum; Dopamine; Dopaminergic Neurons; Fluorine Radioisotopes; Illicit Drugs; Male; Mice, Inbred BALB C; Neuroimaging; Positron-Emission Tomography; Radiography; Radiopharmaceuticals
PubMed: 24877059
DOI: 10.1155/2014/157923 -
Scientific Reports Apr 2021It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life....
It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [F]-Fluoro-2-deoxy-2-D-glucose (F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring F-FDG accumulation and F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.
Topics: Age Factors; Animals; Autoradiography; Brain; Carbohydrate Metabolism; Fluorodeoxyglucose F18; Glucose; Insulin; Male; Mice; Organ Specificity
PubMed: 33795778
DOI: 10.1038/s41598-021-86825-8 -
Pharmacology Research & Perspectives Apr 2022Previously published digital autoradiography of H-labeled capecitabine reveals a near-uniform distribution of activity throughout a murine pancreatic model. This is in...
Analysis of capecitabine metabolites in conjunction with digital autoradiography in a murine model of pancreatic cancer suggests extensive drug penetration through the tumor.
Previously published digital autoradiography of H-labeled capecitabine reveals a near-uniform distribution of activity throughout a murine pancreatic model. This is in contrast both to C-labeled gemcitabine, and established expectations, as the dense stroma of pancreatic cancer is understood to inhibit drug penetration. Capecitabine is a pro-drug for 5 FU. The positioning of the radiolabel on capecitabine leaves open the possibility that much of the autoradiographic signal is generated by nontoxic compounds. Studies were performed on tumors derived via organoid culture from a murine KPC tumor. As before, we performed autoradiography comparing H capecitabine to the gemcitabine analog F-FAC. The metabolism of capecitabine in this model was studied through LC-MS of tumor tissue. The autoradiographs confirmed that the H label from capecitabine was much more uniformly distributed through the tumor than the F from the gemcitabine analog. LC-MS revealed that approximately 75% of the molar mass of capecitabine had been converted into 5 FU or pre-5 FU compounds. The remainder had been converted into nontoxic species. Therapeutically relevant capecitabine metabolites achieve a relatively even distribution in this pancreatic cancer model, in contrast to the gemcitabine analog F-FAC. In a human xenograft model, (BxPC3), the H label from capecitabine was also uniformly spread across the tumor autoradiographs. However, at 2 h post-administration the metabolism of capecitabine had proceeded further and the bulk of the agent was in the form of nontoxic species.
Topics: Animals; Autoradiography; Capecitabine; Disease Models, Animal; Humans; Mice; Pancreatic Neoplasms; Prodrugs
PubMed: 35257504
DOI: 10.1002/prp2.898 -
Kidney International Jul 1996The cellular localization of endothelin receptors in the inner medulla of the rat kidney was investigated by using high resolution light and electron microscopic...
The cellular localization of endothelin receptors in the inner medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography, with the microwave irradiation fixation methods. Kidney slices were incubated with 125I-endothelin-1 alone or with selective ligands for the endothelin ETB and/or ETA receptors for light microscopic autoradiography. At the microscopic level, 125I-endothelin-1 was found to bind specifically to the glomeruli, arterioles and peritubular spaces in the cortex and vasa recta and surrounding tissues in the inner medulla. These bindings were also observed when the tissue slices were incubated in the presence of IRL1620 (ETB receptor agonist) or 97-139 (ETA receptor antagonist). Electron microscopic autoradiography using 125I-endothelin-1 in the inner medulla revealed silver grains over endothelial cells of the vasa recta and interstitial and collecting duct cells. No grains were detected over inner lining cells of the thin limbs of Henle's loop. These interstitial cells contained abundant microorganelles and lipid droplets, and had extensive cytoplasmic processes that closely related to the basement membranes of the vasa recta and loop of Henle. These findings demonstrate that type 1 interstitial cells are also primary sites for endothelin receptors as well as endothelial cells of the vasa recta and collecting duct cells in the inner medulla.
Topics: Animals; Autoradiography; Kidney Medulla; Male; Microscopy, Electron; Rats; Rats, Wistar; Receptors, Endothelin
PubMed: 8807582
DOI: 10.1038/ki.1996.296 -
BioTechniques Aug 1996This study demonstrates the use of phosphor-screen autoradiography as a means of measuring cell adhesion and cell expansion on polymer surfaces. The method has... (Comparative Study)
Comparative Study
This study demonstrates the use of phosphor-screen autoradiography as a means of measuring cell adhesion and cell expansion on polymer surfaces. The method has particular merit in cases where a specific substrate may be opaque or biochemically incompatible with colorimetric assay methodologies. With the phosphor-screen autoradiography method, there was a linear relationship between cell number and quantitated radioactivity. The technique has also been validated by comparison with a colorimetric assay of adhesion conducted for attachment to conventional culture substrata. The data supported the view that the use of phosphor-screen autoradiography was a valid method for detecting cell attachment, and it gave equivalent results to the colorimetric assay. Furthermore, a comparison between phosphor-screen autoradiography and a dye-staining method showed that this technique can be used as a means of quantifying cellular expansion over surfaces.
Topics: Autoradiography; Biocompatible Materials; Cell Adhesion; Cell Movement; Colorimetry; Coloring Agents; Image Processing, Computer-Assisted; Luminescent Measurements; Methylene Blue; Sensitivity and Specificity; Staining and Labeling; Surface Properties
PubMed: 8862816
DOI: 10.2144/96212rr04 -
Journal of Lipid Research Jan 2002The rates of synthesis, turnover, and half-lives were determined for brain microsomal ether phospholipids in the awake adult unanesthetized rat. A multicompartmental...
The rates of synthesis, turnover, and half-lives were determined for brain microsomal ether phospholipids in the awake adult unanesthetized rat. A multicompartmental kinetic model of phospholipid metabolism, based on known pathways of synthesis, was applied to data generated by a 5 min intravenous infusion of [1,1-(3)H]hexadecanol. At 2 h post-infusion, 29%, 33%, and 31% of the total labeled brain phospholipid was found in the 1-O-alkyl-2-acyl-sn-glycero-3-phosphate, ethanolamine, and choline ether phospholipid fractions, respectively. Autoradiography and membrane fractionation showed that 3% of the net incorporated radiotracer was in myelin at 2 h, compared to 97% in gray matter microsomal and synaptosomal fractions. Based on evidence that ether phospholipid synthesis occurs in the microsomal membrane fraction, we calculated the synthesis rates of plasmanylcholine, plasmanylethanolamine, plasmenylethanolamine, and plasmenylcholine equal to 1.2, 9.3, 27.6, and 21.5 nmol. g(-1). min(-1), respectively. Therefore, 8% of the total brain ether phospholipids have half-lives of about 36.5, 26.7, 23.1, and 15.1 min, respectively. Furthermore, we clearly demonstrate that there are at least two pools of ether phospholipids in the adult rat brain. One is the static myelin pool with a slow rate of tracer incorporation and the other is a dynamic pool found in gray matter. The short half-lives of microsomal ether phospholipids and the rapid transfer to synaptosomes are consistent with evidence of the marked involvement of these lipids in brain signal transduction and synaptic function.
Topics: Animals; Autoradiography; Biological Transport; Brain; Choline; Ethanolamine; Fatty Alcohols; Half-Life; Male; Microsomes; Phospholipid Ethers; Rats; Rats, Sprague-Dawley; Synaptosomes
PubMed: 11792723
DOI: No ID Found -
Upsala Journal of Medical Sciences Aug 2014The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET)...
OBJECTIVE
The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET) is a potentially valuable instrument for non-invasive in vivo pathophysiological studies. No specific tracer to identify the pathophysiological process of aneurysmal dilatation is yet available, however. The aim of this study was to explore if different PET tracers could be useful to image aneurysmal disease.
METHODS AND RESULTS
Human aneurysmal aortic tissue, collected during elective resection of abdominal aortic aneurysm (AAA) of asymptomatic patients, was investigated in vitro by means of autoradiography with [(68)Ga]CRP-binder targeting C-reactive protein, [(11)C]DAA1106 targeting translocator protein (18 kDa), [(11)C]D-deprenyl with unknown target receptor, [(11)C]deuterium-L-deprenyl targeting astrocytes, [(18)F]fluciclatide targeting integrin αVβ3, [(68)Ga]IMP461 and bi-specific antibody TF2 052107 targeting carcinoembryonic antigen, [(18)F]F-metomidate targeting mitochondrial cytochrome P-450 species in the adrenal cortex, and [(18)F]vorozole targeting aromatase. Of the investigated tracers, only [(18)F]fluciclatide exhibited specific binding, whereas the other PET tracers failed to show specific uptake in the investigated tissue and are probably not useful for the intended purpose.
CONCLUSION
It seems likely that αVβ3 integrin expression in AAA can be visualized with PET and that the αVβ3 selective tracer, [(18)F]fluciclatide, may be suitable for in vivo molecular imaging of asymptomatic AAA. Additional evaluation of [(18)F]fluciclatide and αVβ3 integrin expression in AAA will be performed in vitro as well as in vivo.
Topics: Aged; Aortic Aneurysm, Abdominal; Autoradiography; Humans; Male; Positron-Emission Tomography
PubMed: 24555564
DOI: 10.3109/03009734.2014.894157 -
The Journal of Cell Biology Feb 1978It is well known that ouabain, a specific inhibitor of Na-K ATPase-dependent transport, interferes with renal tubular salt reabsorption. In this study, we employed...
It is well known that ouabain, a specific inhibitor of Na-K ATPase-dependent transport, interferes with renal tubular salt reabsorption. In this study, we employed radiochemical methods to measure the kinetics of [3H]ouabain binding to slices of rabbit renal medulla and high resolution quantitative autoradiography to determine the location and number of cellular binding sites. The kinetics obeyed a simple bimolecular reaction with an association constant of 2.86 +/- 0.63 SD x 10(3) M-1 min-1 and a dissociation constant of 1.46 x 10(-3) min-1, yielding an equilibrium binding constant of 0.51 x 10(-6) M. Binding was highly dependent upon temperature. At a concentration of 10(-6) M, the rate of accumulation between 25 degrees C and 35 degrees C exhibited a Q10 of 1.8. At 0 degree C the rate of ouabain dissociation was negligible. The specificity of binding was demonstrated with increasing potassium concentrations. At a concentration of 1 microM, 6 mM, and 50 mM K+ produced a 2.5- and 7-fold decrease, respectively, in the rate of ouabain accumulation observed at zero K+. Binding was completely inhibited by 1 mM strophanthin K. The major site of ouabain binding was the thick ascending limb; little or no binding was observed in thin limbs and collecting ducts. Moreover, binding was confined to the basolateral membranes. From autoradiographic grain density measurements, it was estimated that each cell contains over 4 x 10(6) ouabain binding sites or Na-K ATPase molecules. These results taken together with physiological and biochemical observations suggest that Na-K ATPase plays a key role in salt reabsorption by this segment.
Topics: Animals; Autoradiography; Female; Kidney Medulla; Kidney Tubules; Kinetics; Ouabain; Rabbits; Tritium
PubMed: 10605438
DOI: 10.1083/jcb.76.2.278 -
Chemosphere Sep 2011Copepods have been widely used to evaluate toxicity of metals present in marine environments. However, a technical difficulty is to understand the possible routes of...
Copepods have been widely used to evaluate toxicity of metals present in marine environments. However, a technical difficulty is to understand the possible routes of metal uptake and to identify in which tissues or organs metals are being accumulated. Traditional techniques are hard to be employed once each organ has to be analyzed separately. Autoradiography is an alternative technique to circumvent this limitation, since metal distribution in tissues can be visualized and quantified, even in small organisms like copepods. In the present study, accumulation and distribution of (64)Cu in the copepod Calanus hyperboreus was studied using autoradiography. Copepods were exposed for 2 h to copper (2.3 mg L(-1); 1.08 MBq (64)Cu mg(-1) Cu) and then allowed to depurate for 2 h in clean seawater. Total (64)Cu was determined by gamma-spectrometry after a metal exposure and a depuration period. (64)Cu distribution was determined based on images generated by autoradiography. Metal accumulation was observed on all external surfaces of the copepods, being accumulated mostly on the ventral region, followed by dorsal, urossoma and internal regions. After depuration, radioactivity levels had a decrease in the sum of external body surface. Our results show that copper uptake by C. hyperboreus is fast and that a non-negligible proportion of the accumulated metal can reach internal tissues, which may lead to detrimental physiological effects. Moreover, whole-body autoradiography was demonstrated to be an efficient technique to study copper accumulation and body distribution in a very small organism such as the copepod C. hyperboreus.
Topics: Animals; Autoradiography; Copper; Copper Radioisotopes; Crustacea; Tissue Distribution; Water Pollutants, Chemical; Whole Body Imaging
PubMed: 21741674
DOI: 10.1016/j.chemosphere.2011.06.065 -
American Journal of Human Genetics Nov 1977A novel technique for detecting electrophoretic and quantitative variants of group-specific component (Gc) proteins is described. The technique, in vitro labeling with...
A novel technique for detecting electrophoretic and quantitative variants of group-specific component (Gc) proteins is described. The technique, in vitro labeling with radioactive vitamin D followed by polyacrylamide gel electrophoresis and autoradiography (PAGE autoradiography), permits sensitive, high resolution detection of Gc variants by virtue of a physiologically significant property: the ability of Gc to bind vitamin D and 25-hydroxyvitamin D. Using this procedure, anodal Gc variants, with mobility similar to Gc Aborigine and Gc Eskimo, were observed in Chinese, Japanese, African Pygmies, and American Blacks. The gene frequency of these variants ranges from 2.6% to 15%; they were not previously known to be polymorphic in these populations. In addition to qualitative variants, individual variation in Gc band density ratios is documented and discussed. These studies not only illustrate the utility of PAGE autoradiography in screening Gc, but also confirm that a major functional role of Gc in man and other animals is the transport of vitamin D and vitamin D metabolites.
Topics: Adult; Alpha-Globulins; Asian People; Autoradiography; Black People; Blood Protein Electrophoresis; Electrophoresis, Polyacrylamide Gel; Genetic Variation; Humans; Radioisotopes; Radioligand Assay; Vitamin D; White People
PubMed: 73350
DOI: No ID Found