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The AAPS Journal Mar 2010Whole-body autoradiography ((WBA) or quantitative WBA (QWBA)), microautoradiography (MARG), matrix-assisted laser desorption/ionization mass spectrometric imaging... (Review)
Review
Whole-body autoradiography ((WBA) or quantitative WBA (QWBA)), microautoradiography (MARG), matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), and secondary ion mass spectrometric imaging (SIMS-MSI) are high-resolution, molecular imaging techniques used to study the tissue distribution of radiolabeled and nonlabeled compounds in ex vivo, in situ biological samples. WBA, which is the imaging of the whole-body of lab animals, and/or their organ systems; and MARG, which provides information on the localization of radioactivity in histological preparations and at the cellular level, are used to support drug discovery and development efforts. These studies enable the conduct of human radiolabeled metabolite studies and have provided pharmaceutical scientists with a high resolution and quantitative method of accessing tissue distribution. MALDI-MSI is a mass spectrometric imaging technique capable of label-free and simultaneous determination of the identity and distribution of xenobiotics and their metabolites as well as endogenous substances in biological samples. This makes it an interesting extension to WBA and MARG, eliminating the need for radiochemistry and providing molecular specific information. SIMS-MSI offers a complementary method to MALDI-MSI for the acquisition of images with higher spatial resolution directly from biological specimens. Although traditionally used for the analysis of surface films and polymers, SIMS has been used successfully for the study of biological tissues and cell types, thus enabling the acquisition of images at submicrometer resolution with a minimum of samples preparation.
Topics: Animals; Autoradiography; Drug Discovery; Humans; Image Processing, Computer-Assisted; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrometry, Mass, Secondary Ion
PubMed: 19921438
DOI: 10.1208/s12248-009-9158-4 -
CA: a Cancer Journal For Clinicians 1958
Topics: Autoradiography; Humans
PubMed: 13596897
DOI: 10.3322/canjclin.8.5.170 -
Neuroscience Letters Jan 2019Dopamine D3 receptors have key roles in behavioral reward, addiction, Parkinson's disease, and schizophrenia, and there is interest in studying their role in these... (Review)
Review
Dopamine D3 receptors have key roles in behavioral reward, addiction, Parkinson's disease, and schizophrenia, and there is interest in studying their role in these disorders using PET. However, current PET radiotracers for studying D3 receptors in humans all bind to both D2 and D3 due to similarities between the two receptors. Selective D2 and D3 radioligands would aid investigation of the differences between D2 and D3 circuitry in the central nervous system. While there are currently in vitro measures of ligand D3/D2 selectivity, there is a need for an in vivo PET measure of D3/D2 selectivity. This review discusses current PET imaging of dopamine D2/D3 receptors and proposes methodology for quantitating in vivo selectivity of probes for PET imaging of dopamine D3 receptors.
Topics: Autoradiography; Carbon Radioisotopes; Fluorine Radioisotopes; Humans; Ligands; Positron-Emission Tomography; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 29518538
DOI: 10.1016/j.neulet.2018.03.006 -
Journal of Nuclear Medicine : Official... Apr 2022Digital autoradiography (DAR) is a powerful tool to quantitatively determine the distribution of a radiopharmaceutical within a tissue section and is widely used in drug...
Digital autoradiography (DAR) is a powerful tool to quantitatively determine the distribution of a radiopharmaceutical within a tissue section and is widely used in drug discovery and development. However, the low image resolution and significant background noise can result in poor correlation, even errors, between radiotracer distribution, anatomic structure, and molecular expression profiles. Differing from conventional optical systems, the point-spread function in DAR is determined by properties of radioisotope decay, phosphor, and digitizer. Calibration of an experimental point-spread function a priori is difficult, prone to error, and impractical. We have developed a content-adaptive restoration algorithm to address these problems. We model the DAR imaging process using a mixed Poisson-gaussian model and blindly restore the image by a penalized maximum-likelihood expectation-maximization algorithm (PG-PEM). PG-PEM implements a patch-based estimation algorithm with density-based spatial clustering of applications with noise to estimate noise parameters and uses L2 and Hessian Frebonius norms as regularization functions to improve performance. First, PG-PEM outperformed other restoration algorithms at the denoising task ( 0.01). Next, we implemented PG-PEM on preclinical DAR images (F-FDG, treated mouse tumor and heart; F-NaF, treated mouse femur) and clinical DAR images (bone biopsy sections from RaCl-treated castration-resistant prostate cancer patients). DAR images restored by PG-PEM of all samples achieved a significantly higher effective resolution and contrast-to-noise ratio and a lower SD of background ( 0.0001). Additionally, by comparing the registration results between the clinical DAR images and the segmented bone masks from the corresponding histologic images, we found that the radiopharmaceutical distribution was significantly improved ( 0.0001). PG-PEM is able to increase resolution and contrast while robustly accounting for DAR noise and demonstrates the capacity to be widely implemented to improve preclinical and clinical DAR imaging of radiopharmaceutical distribution.
Topics: Algorithms; Animals; Autoradiography; Diagnostic Imaging; Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Male; Mice; Phantoms, Imaging; Radiopharmaceuticals; Tissue Distribution
PubMed: 34385337
DOI: 10.2967/jnumed.121.262270 -
Methods (San Diego, Calif.) Apr 2016In situ hybridization is the technique by which specific RNA or DNA molecules are detected in cytological preparations. Basically it involves formation of a hybrid... (Review)
Review
In situ hybridization is the technique by which specific RNA or DNA molecules are detected in cytological preparations. Basically it involves formation of a hybrid molecule between an endogenous single-stranded RNA or DNA in the cell and a complementary single-stranded RNA or DNA probe. In its original form the probe was labeled with (3)H and the hybrid was detected by autoradiography. The first successful experiments in 1968 involved detection of the highly amplified ribosomal DNA in oocytes of the frog Xenopus, followed soon after by the reiterated "satellite DNA" in mouse and Drosophila chromosomes. Fluorescent probes were developed about ten years later.
Topics: Animals; Autoradiography; DNA; DNA Probes; Drosophila melanogaster; Fluorescent Dyes; History, 20th Century; History, 21st Century; In Situ Hybridization; Larva; Mice; Oocytes; Polytene Chromosomes; RNA; Salivary Glands; Tritium; Xenopus laevis
PubMed: 26655524
DOI: 10.1016/j.ymeth.2015.11.026 -
Radiation Oncology (London, England) Jun 2012The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography... (Comparative Study)
Comparative Study
BACKGROUND
The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas.
METHODS
Biopsies were collected from individual tumors between approximately 3 and 25 hours after the intravenous injection of (64)Cu-ATSM and pimonidazole. (64)Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired (64)Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. (64)Cu-ATSM and (18)FDG PET/CT scans were performed in a concurrent study and uptake characteristics were obtained for tumors where available.
RESULTS
Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-ATSM. In the case of the latter, uptake at scans performed 3 h post injection (pi) generally showed strong positive correlated to pimonidazole uptake.Comparison of distribution patterns of pimonidazole immunohistochemistry and (64)Cu-ATSM autoradiography yielded varying results. Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers.
CONCLUSIONS
Tumors with high levels of pimonidazole staining generally displayed high uptake of (18)FDG and (64)Cu-ATSM (3 h pi.). Similar regional distribution of (64)Cu-ATSM and pimonidazole was observed in most heterogeneous tumor regions. However, tumor and hypoxia level dependent differences may exist with regard to the hypoxia specificity of (64)Cu-ATSM in canine tumors.
Topics: Animals; Autoradiography; Carcinoma; Cell Hypoxia; Coordination Complexes; Copper Radioisotopes; Dogs; Fluorodeoxyglucose F18; Immunohistochemistry; Nitroimidazoles; Organometallic Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Sarcoma; Thiosemicarbazones
PubMed: 22704363
DOI: 10.1186/1748-717X-7-89 -
Metabolic Brain Disease Jun 2015The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study... (Review)
Review
The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study cerebral glucose metabolism with a focus on those used in clinical TBI studies. Arterio-venous measurements provide a global measure of glucose uptake into the brain. Microdialysis allows the in vivo sampling of brain extracellular fluid and is well suited to the longitudinal assessment of metabolism after TBI in the clinical setting. A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked. Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed. We summarise the data published from these techniques and review their potential uses in the clinical setting.
Topics: Animals; Autoradiography; Brain Injuries; Energy Metabolism; Extracellular Fluid; Glucose; Humans; Magnetic Resonance Imaging; Microdialysis; Positron-Emission Tomography
PubMed: 25413449
DOI: 10.1007/s11011-014-9628-y -
PloS One 2017This work presents a comparison of three autoradiography techniques for imaging biological samples contaminated with actinides: emulsion-based, plastic-based... (Comparative Study)
Comparative Study
This work presents a comparison of three autoradiography techniques for imaging biological samples contaminated with actinides: emulsion-based, plastic-based autoradiography and a quantitative digital technique, the iQID camera, based on the numerical analysis of light from a scintillator screen. In radiation toxicology it has been important to develop means of imaging actinide distribution in tissues as these radionuclides may be heterogeneously distributed within and between tissues after internal contamination. Actinide distribution determines which cells are exposed to alpha radiation and is thus potentially critical for assessing absorbed dose. The comparison was carried out by generating autoradiographs of the same biological samples contaminated with actinides with the three autoradiography techniques. These samples were cell preparations or tissue sections collected from animals contaminated with different physico-chemical forms of actinides. The autoradiograph characteristics and the performances of the techniques were evaluated and discussed mainly in terms of acquisition process, activity distribution patterns, spatial resolution and feasibility of activity quantification. The obtained autoradiographs presented similar actinide distribution at low magnification. Out of the three techniques, emulsion autoradiography is the only one to provide a highly-resolved image of the actinide distribution inherently superimposed on the biological sample. Emulsion autoradiography is hence best interpreted at higher magnifications. However, this technique is destructive for the biological sample. Both emulsion- and plastic-based autoradiography record alpha tracks and thus enabled the differentiation between ionized forms of actinides and oxide particles. This feature can help in the evaluation of decorporation therapy efficacy. The most recent technique, the iQID camera, presents several additional features: real-time imaging, separate imaging of alpha particles and gamma rays, and alpha activity quantification. The comparison of these three autoradiography techniques showed that they are complementary and the choice of the technique depends on the purpose of the imaging experiment.
Topics: Actinoid Series Elements; Alpha Particles; Animals; Autoradiography; Lung; Muscle, Skeletal; Rats; Skin
PubMed: 29023595
DOI: 10.1371/journal.pone.0186370 -
Nuclear Medicine Communications Sep 2021This study aimed to evaluate the distribution of Astatine-211 (211At) solution dispersion in a small animal cage using autoradiography imaging to simulate the dispersion...
OBJECTIVE
This study aimed to evaluate the distribution of Astatine-211 (211At) solution dispersion in a small animal cage using autoradiography imaging to simulate the dispersion of 211At in a lab room to eventually prevent user's risk of internal exposure in terms of radiation safety.
METHODS
211At radiation sources with two chemical properties (Na211At and Free 211At) were prepared. The solutions of 211At were placed onto a dish with paper, and then, it was placed in a small animal cage for 3 h. After removing the dish, an imaging plate with attaching reference sources was placed at four walls of the cage for 15 h in a lead box. Imaging plates were read, and all pixel data were calculated using Microsoft Excel 2016 to obtain three-dimensional (3D) distribution. Calculated results were depicted using a 3D sphere model.
RESULTS
The mean activity of Free 211At was 2.3 times higher than that of Na211At on all autoradiography images. In the cage, the shape of the dispersion of Na211At was almost homogeneous, whereas that of Free 211At was more heterogeneous.
CONCLUSION
We found that the solution of 211At vaporized naturally and was distributed heterogeneously in the cage, and the chemical properties of 211At influenced their behaviors. These results must be considered to minimize the risks of radiation safety.
Topics: Astatine; Autoradiography; Humans; Radioimmunotherapy
PubMed: 34001828
DOI: 10.1097/MNM.0000000000001430 -
BMJ Open Diabetes Research & Care Apr 2021Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2...
INTRODUCTION
Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans.
RESEARCH DESIGN AND METHODS
GLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract.
RESULTS
High homogenous uptake of Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of Ga-exendin-4 in pigs scanned by PET.
CONCLUSION
We identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models.
Topics: Animals; Autoradiography; Diabetes Mellitus, Type 2; Gastrointestinal Tract; Glucagon-Like Peptide 1; Pancreas; Swine; Tissue Distribution
PubMed: 33903116
DOI: 10.1136/bmjdrc-2020-002083