sodium-pertechnetate-tc-99m and Disease-Models--Animal

Topics: Allografts; Animals; Apoptosis; Bacteriocins; Disease Models, Animal; Feasibility Studies; Graft Rejection; Heart Transplantation; Mice, Inbred BALB C; Molecular Imaging; Myocardium; Peptides; Predictive Value of Tests; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography; Sodium Pertechnetate Tc 99m

The present study aimed to develop a stable Graves' disease (GD) model in BALB/c mice by immunization and electroporation (EP). A total of 90 mice were divided into experimental (n=50), control (n=20) and blank (n=20) groups. The recombinant plasmid pcDNA3.1/thyroid‑stimulating hormone (TSH) receptor 268 was constructed and injected into the bilateral gastrocnemius of experimental group mice at weeks 1, 4, 7 and 10. Equal volumes of saline were injected into the control and blank groups at the same time. The experimental and control groups were subjected to EP at the same time and location to enhance immunization. The levels of total serum thyroxine (T4) and serum TSH were examined by radioimmunoassay and immunoradiometric assay, respectively. The levels of serum thyrotropin receptor N‑terminal (TRAb N) and C‑terminal (TRAb C) antibodies were assessed by ELISA. Whole body pertechnetate (99mTcO4‑) imaging was performed. Mouse weight and thyroid morphology and pathology were analyzed. The GD BALB/c mouse model was successfully established, with a positive rate of 79.17% (38/48). T4 levels increased from baseline levels of 12.05±4.23 to 52.51±23.58 ng/ml by week 12 (P<0.0001). TSH levels decreased from baseline levels of 5.53±2.78 to 1.43±0.89 µIU/ml by week 12 (P<0.0001). TRAb N antibody levels increased from baseline levels of 0.006±0.002 to 0.278±0.106 mIU/ml by week 12 (P<0.0001). TRAb C antibody levels increased from baseline levels of 11.111±2.808 to 46.701±26.436 arbitrary units/ml by week 12 (P<0.0001). At week 21, TSH levels remained reduced compared with pre‑immunization levels (P<0.0001). Although T4, and TRAb N and C levels decreased, they remained increased compared with preimmunization levels (P<0.0001, P<0.0001, P=0.001). There were no significant alterations in antibody levels between the control and blank groups. Following four immunizations, the uptake of 99mTcO4‑ by the thyroid was significantly increased in the experimental group. The mean weight of the experimental mice was significantly reduced compared with the control and blank groups (all P<0.0001). Furthermore, the thyroid glands of the immunized mice were enlarged and exhibited lymphocyte infiltration, fewer colloid nodules and an increased height of epithelial cells. In conclusion, by injecting recombinant plasmid pcDNA3.1/TSHR268 and EP, a GD mouse model was successfully established.

Topics: Animals; Disease Models, Animal; Female; Graves Disease; Humans; Immunization; Mice, Inbred BALB C; Organ Size; Receptors, Thyrotropin; Sodium Pertechnetate Tc 99m; Thyroid Gland; Thyrotropin; Thyroxine

To assess the potential utility of an integrin αvβ3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model.. All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5).. Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvβ3 on the activated hepatic stellate cells, and the integrin αvβ3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001).. (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis.

Topics: Animals; Disease Models, Animal; Imaging, Three-Dimensional; Integrin alphaVbeta3; Liver Cirrhosis; Male; Multimodal Imaging; Radiopharmaceuticals; Rats; Rats, Wistar; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon; Tomography, Spiral Computed

Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification. hNIS is a glycoprotein that naturally transports iodide (I-) into thyroid cells and has the ability to symport the radiotracer 99mTc-pertechnetate (99mTcO4-). A549 lung adenocarcinoma cells were genetically modified with plasmid or lentiviral vectors to express hNIS. Modified cells were implanted into athymic nude mice to develop two tumor models: a subcutaneous and an orthotopic xenograft tumor model. Tumor progression was longitudinally imaged using SPECT/CT and quantified by SPECT voxel analysis. hNIS expression in lung tumors was analyzed by quantitative real-time PCR. Additionally, hematoxylin and eosin staining and visual inspection of pulmonary tumors was performed. We observed that lentiviral transduction provided enhanced and stable hNIS expression in A549 cells. Furthermore, 99mTcO4- uptake and accumulation was observed within lung tumors allowing for imaging and quantification of tumor mass at two-time points. This study illustrates the development of an orthotopic lung cancer model that can be longitudinally imaged throughout the experimental timeline thus avoiding inter-animal variability and leading to a reduction in total animal numbers. Furthermore, our orthotopic lung cancer animal model is clinically relevant and the genetic modification of cells for SPECT/CT imaging can be translated to other tissue-specific tumor animal models.

Topics: A549 Cells; Animals; Cell Line, Tumor; Disease Models, Animal; Iodides; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Sodium Pertechnetate Tc 99m; Symporters; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Transplantation, Heterologous; Tumor Burden

The present work evaluated whether the prepared nanoparticles (NPs) would be able to target the drug to the brain by a non-invasive nasal route enhancing its bioavailability.. Bromocriptine (BRC) chitosan NPs (CS NPs) were prepared by ionic gelation method. The biodistribution, pharmacokinetic parameters and dopamine concentration was analysed by ultra-HPLC/mass spectrometry method. The histopathological examination in haloperidol-induced Parkinson's disease in mice model following intranasal (i.n.) administration was evaluated.. BRC was found stable in all exposed conditions and the percentage accuracy observed for intra-day and inter-day batch samples ranged from 90.5 to 107% and 95.3 to 98.9% for plasma and brain homogenates, respectively. BRC-loaded CS NPs showed greater retention into the nostrils (42 ± 8.5% radioactivity) for about 4 h, whereas the 44 ± 7.5% could be retained up to 1 h for BRC solution. The brain:blood ratios of 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05 of BRC-loaded CS NPs (i.n.) > BRC solution (i.n.) > BRC-loaded CS NPs (intravenous), respectively, at 0.5 h indicated direct nose-to-brain transport bypassing blood-brain barrier. BRC-loaded CS NPs administered intranasally showed significantly high dopamine concentration (20.65 ± 1.08 ng/ml) as compared to haloperidol-treated mice (10.94 ± 2.16 ng/ml) (p < 0.05). Histopathology of brain sections showed selective degeneration of the dopaminergic neurons in haloperidol-treated mice which was markedly reverted by BRC-loaded CS NPs.. Nanoparticulate drug delivery system could be potentially used as a nose-to-brain drug delivery carrier for the treatment of Parkinson's disease.

Topics: Administration, Intranasal; Animals; Antiparkinson Agents; Biological Availability; Biological Transport; Blood-Brain Barrier; Brain; Bromocriptine; Chitosan; Chromatography, High Pressure Liquid; Disease Models, Animal; Dopamine; Drug Delivery Systems; Female; Male; Mass Spectrometry; Mice; Nanoparticles; Nasal Mucosa; Parkinson Disease; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Tissue Distribution

Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes.. The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtained by firefly luciferase and human sodium-iodide symporter labeling of cardiosphere-derived cells were investigated.. (18)Fluorodeoxyglucose uptake, ATP levels, (99m)Tc-pertechnetate uptake, and bioluminescence were measured in vitro in adherent and suspended cardiosphere-derived cells. In vivo dual-isotope single-photon emission computed tomography/computed tomography imaging or bioluminescence imaging (BLI) was performed 1 hour and 24 hours after cardiosphere-derived cell transplantation. Single-photon emission computed tomography quantification was performed using a phantom for signal calibration. Cell loss between 1 hour and 24 hours after transplantation was quantified by quantitative polymerase chain reaction and ex vivo luciferase assay. Cell dissociation followed by suspension for 1 hour resulted in decreased glucose uptake, cellular ATP, (99m)Tc uptake, and BLI signal by 82%, 43%, 42%, and 44%, respectively, compared with adherent cells, in vitro. In vivo (99m)Tc uptake was significantly lower at 1 hour compared with 24 hours after cell transplantation in the noninfarct (P<0.001; n=3) and infarct (P<0.001; n=4) models, despite significant cell loss during this period. The in vivo BLI signal was significantly higher at 1 hour than at 24 hours (P<0.01), with the BLI signal being higher when cardiosphere-derived cells were suspended in glucose-containing medium compared with saline (PBS).. Adhesion is an important determinant of cellular bioenergetics, (99m)Tc-pertechnetate uptake, and BLI signal. BLI and sodium-iodide symporter imaging may be useful for in vivo optimization of bioenergetics in transplanted cells.

Topics: Adenosine Triphosphate; Animals; Cell Adhesion; Cell Tracking; Disease Models, Animal; Energy Metabolism; Fluorodeoxyglucose F18; Gene Expression Regulation; Genes, Reporter; Humans; Image Processing, Computer-Assisted; Luciferases, Firefly; Luminescent Measurements; Male; Multimodal Imaging; Myocardial Infarction; Myocytes, Cardiac; Polymerase Chain Reaction; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Inbred WKY; Signal Processing, Computer-Assisted; Sodium Pertechnetate Tc 99m; Spheroids, Cellular; Symporters; Time Factors; Tomography, X-Ray Computed; Transfection

The primary aim of this study was to investigate the potential use of chitosan nanoparticles as a delivery system to enhance the brain targeting efficiency of bromocriptine (BRC) following intranasal (i.n.) administration. The BRC loaded chitosan nanoparticles (CS NPs) were prepared by ionic gelation of CS with tripolyphosphate anions. These NPs had a mean size (161.3 ± 4. 7 nm), zeta potential (+40.3 ± 2.7 mV), loading capacity (37.8% ± 1.8%) and entrapment efficiency (84.2% ± 3.5%). The oral administration of haloperidol (2mg/kg) to mice produced typical Parkinson (PD) symptoms. Catalepsy and akinesia outcomes in animals receiving BRC either in solution or within CS NPs showed a reversal in catalepsy and akinesia behavior when compared to haloperidol treated mice, this reversal being specially pronounced in mice receiving BRC loaded CS NPs. Biodistribution of BRC formulations in the brain and blood of mice following i.n. and intravenous (i.v.) administration was performed using optimized technetium labeled (99mTc-labeled) BRC formulations. The brain/blood ratio of 0.47 ± 0.04, 0.69 ± 0.031, and 0.05 ± 0.01 for BRC solution (i.n.), BRC loaded CS NPs (i.n.) and (i.v.) respectively, at 0.5h are suggestive of direct nose to brain transport bypassing the blood-brain barrier. Gamma scintigraphy imaging of mice brain following i.v. and i.n. administrations were performed to determine the localization of drug in brain. The drug targeting index and direct transport percentage for BRC loaded CS NPs following i.n. route were 6.3 ± 0.8 and 84.2% ± 1.9%. These encouraging results confirmed the development of a novel non-invasive nose to brain delivery system of BRC for the treatment of PD.

Topics: Administration, Intranasal; Animals; Antiparkinson Agents; Behavior, Animal; Blood-Brain Barrier; Brain; Bromocriptine; Catalepsy; Chitosan; Disease Models, Animal; Drug Compounding; Drug Delivery Systems; Hypokinesia; Injections, Intravenous; Male; Mice; Nanoparticles; Neurons; Parkinson Disease; Radionuclide Imaging; Random Allocation; Sodium Pertechnetate Tc 99m; Tissue Distribution

This study was designed to determine the antiproliferative effects of combination gene therapy using sodium iodide symporter (NIS)-based radioiodine and lentivirus-mediated short hairpin RNA (shRNA) against hexokinase II (HKII) on vascular smooth muscle cells (VSMCs).. A7r5 rat VSMCs were stably transfected with a dual-expression vector of NIS and Fluc (A7r5-NL cells). Functional assessment was performed by radioiodine uptake assay, luciferase assay and confocal microscopy. After exposure to lentivirus-HKII-shRNA, the (18)F-FDG uptake test and HK activity assay were performed. The effects of combination therapy with (131)I and lentivirus-HKII-shRNA on VSMCs were assessed with an in vitro clonogenic assay. In vivo bioluminescence and nuclear imaging were undertaken using a xenografted mouse model.. In vitro functional assessment confirmed expression of NIS and Fluc genes in A7r5-NL, but not in parent A7r5 cells. Transfection of lentivirus-HKII-shRNA resulted in a significant decrease in messenger RNA expression of the HKII gene, (18)F-FDG uptake and HK activity. The cell survival rate of A7r5-NL decreased to 61.9% and 90.5% by single therapy with 7.4 MBq of (131)I or lentivirus-HKII-shRNA, respectively, and further decreased to 42.9% by combined therapy (P<.05). In vivo bioluminescent and gamma camera images clearly demonstrated optical signals and (99m)Tc pertechnetate uptake at the site of A7r5-NL cell inoculation in nude mice.. The enhanced antiproliferative effect on VSMCs was achieved by a combination of NIS-based radioiodine and lentivirus-mediated HKII shRNA gene therapy. Successful demonstration of in vivo dual reporter gene imaging assures the potential for further application in an animal model.

Topics: Animals; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Genetic Therapy; Hexokinase; Iodine Radioisotopes; Lentivirus; Luciferases; Luminescent Agents; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Radionuclide Imaging; Radiopharmaceuticals; Rats; RNA, Messenger; RNA, Small Interfering; Sodium Pertechnetate Tc 99m; Symporters

In this experimental study on endometriosis, the majority of the implants were successfully detected with technetium-(99mTc) labeled red blood cell scintigraphy.

Topics: Animals; Disease Models, Animal; Endometriosis; Endometrium; Erythrocytes; Female; Iodine Radioisotopes; Peritoneum; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Wistar; Sodium Pertechnetate Tc 99m; Tamoxifen

Hyperthermia may be a consequence of environmental conditions, bacterial or viral infections and/or thyroid storm. This study investigates the acute effect of body temperature elevation on thyroid function and on its scintigraphy studies. Thyroid scintigraphy was performed on New Zealand White rabbits weighing approximately 3-3.5 kg. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99 m pertechnetate ((99m)Tc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Two days later the same protocol was repeated for the same rabbit after increasing the body temperature by 2 degrees C. The experiment was repeated again after a 2-day interval at 3 degrees C, and then after another 2-day interval at 4 degrees C. Plasma free thyroxine (FT(4)), free triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured at control and at different hyperthermic temperatures (+2, 3, 4 degrees C). We recorded isometric tension of rabbit thyroid artery strips in organ baths during stepwise temperature elevation. During hyperthermia the decrease in thyroid function and thyroid scintigraphy studies was proportional to body temperature elevation. The recording of isometric tension in rabbit thyroid artery strips in organ baths showed vasoconstriction during hyperthermia which is proportional to the heating temperature. Plasma FT(4) and FT(3) level were decreased while TSH levels were not affected by acute fever. Our results indicate that hyperthermia causes a transient decrease in thyroid gland function and scintigraphic patterns on radionuclide studies. Thus, body temperatures must be measured before radionuclide studies in order to ensure that interpretation of data is not influenced by hyperthermia.

Topics: Animals; Arteries; Artifacts; Body Temperature; Disease Models, Animal; Down-Regulation; Fever; Male; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Regional Blood Flow; Sodium Pertechnetate Tc 99m; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Vasoconstriction

This study investigated radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously, a (99m)Tc-labeled M13 phage demonstrated specific binding for its host Escherichia coli in vitro and in mice through imaging.. This study was extended to phages P22, E79, VD-13 and phage 60. Each was radiolabeled with (99m)Tc using the chelator MAG(3), and were evaluated for binding to host and non-host bacteria in vitro and in a mouse infection model.. In vitro, each (99m)Tc-phage bound to its host at least 4-fold higher than to non-host bacteria. For example, (99m)Tc-E79 showed 10- to 20-fold greater binding to host Pseudomonas aeruginosa compared to non-host Escherichia coli and Salmonella enterica, and (99m)Tc-phage 60 showed 20-fold greater binding to host Klebsiella pneumoniae over non-hosts. Mice received host or non-host bacteria in one thigh, and 3 h later, the (99m)Tc-phages were administered intravenously. After a further 3 h, the tissues were counted. Liver accumulation was highest for (99m)Tc-E79, averaging 39% compared to an average of 13% for the other (99m)Tc-phages. Animals infected with host bacteria showed infected thigh/normal thigh ratios of 14.2 for (99m)Tc-E79, 2.9 for (99m)Tc-P22, 3.5 for (99m)Tc-VD-13 and 2.1 for (99m)Tc-phage 60.. Although specific host binding was observed in vitro for each of these four (99m)Tc-phages, only (99m)Tc-E79 showed specificity for its host in an in vivo model.

Topics: Animals; Bacteria; Bacterial Infections; Bacteriophages; Disease Models, Animal; Escherichia coli; Host-Pathogen Interactions; Infections; Isotope Labeling; Klebsiella pneumoniae; Male; Mice; Pseudomonas aeruginosa; Radionuclide Imaging; Radiopharmaceuticals; Salmonella enterica; Sodium Pertechnetate Tc 99m; Species Specificity; Tissue Distribution

Annexin V recognizes apoptotic cells by specific molecular interaction with phosphatidyl serine, a lipid that is normally sequestered in the inner leaflet of the cell membrane, but is translocated to the outer leaflet in apoptotic cells, such as foam cells of atherosclerotic plaque. Annexin V could potentially deliver carried materials (such as superparamagnetic contrast agents for magnetic resonance imaging) to sites containing apoptotic cells, such as high grade atherosclerotic lesions, so we administered biochemically-derivatized (annexin V) superparmagnetic iron oxide particles (SPIONs) parenterally to two related rabbit models of human atherosclerosis. We observe development of negative magnetic resonance imaging (MRI) contrast in atheromatous lesions and but not in healthy artery. Vascular targeting by annexin V SPIONs is atheroma-specific (i.e., does not occur in healthy control rabbits) and requires active annexin V decorating the SPION surface. Targeted SPIONs produce negative contrast at doses that are 2,000-fold lower than reported for non-specific atheroma uptake of untargeted superparamagnetic nanoparticles in plaque in the same animal model. Occlusive and mural plaques are differentiable. While most of the dose accumulates in liver, spleen, kidneys and bladder, annexin V SPIONs also partition rapidly and deeply into early apoptotic foamy macrophages in plaque. Contrast in plaque decays within 2 months, allowing MRI images to be replicated with a subsequent, identical dose of annexin V SPIONs. Thus, biologically targeted superparamagnetic contrast agents can contribute to non-invasive evaluation of cardiovascular lesions by simultaneously extracting morphological and biochemical data from them.

Topics: Animals; Annexin A5; Aorta, Abdominal; Atherosclerosis; Contrast Media; Dextrans; Disease Models, Animal; Ferrosoferric Oxide; Humans; Iron; Magnetic Resonance Imaging; Magnetite Nanoparticles; Metal Nanoparticles; Oxides; Particle Size; Rabbits; Sodium Pertechnetate Tc 99m; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The aim of this study was to correlate structural, histomorphological damage of the salivary gland with scintigraphic findings during fractioned radiotherapy.. The head and neck area of 27 WAG/RijH rats was irradiated with (60)Co-gamma-rays (60 Gy/30f/6 weeks). A port-system was implanted and (99m)Tc-pertechnetat applied at different stages of irradiation (0, 16, 30, 46, 60 Gy and 6 months post irradiation).. After the application of 16 Gy an intra- and extra-cellular oedema developed in the salivary glands. The progressive vacuolisation (30 Gy) passed over into lipomatosis (46 Gy) and necrosis (60 Gy) in the parotid and mandibular glands. Six months after irradiation treatment, the chronic histomorphological damage corresponded to stage II according to Seifert. The corresponding loss in gland function was 13% (16 Gy); 26% (30 Gy); 57% (46 Gy); 75% (60 Gy) and 66.5% (6 months post irradiation).. This animal model demonstrates the correlation between histomorphological and scintigraphic findings.

Topics: Animals; Cobalt Radioisotopes; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Lipomatosis; Male; Parotid Gland; Radiation Injuries, Experimental; Radiation-Protective Agents; Radioisotope Teletherapy; Radionuclide Imaging; Rats; Rats, Inbred Strains; Salivary Glands; Sodium Pertechnetate Tc 99m; Statistics as Topic; Submandibular Gland

Xerostomia is the most debilitating side effect induced by irradiation of head and neck tumours and is caused by irradiation damage to the salivary glands. The aim of this study was to correlate structural histomorphological damages and sialoscintigraphical findings during fractioned radiotherapy. The head and neck area of 27 WAG/RijH rats was irradiated with 60Co-gamma rays (60 Gy/30f 6 weeks). To evaluate salivary gland function, a port system was implanted, and 99mTc-pertechnetate was applied at different stages of irradiation (0, 16, 30, 46, 60 and 6 months post-irradiation). In the course of treatment the parotid glands were examined histopathologically. Rat salivary glands developed a dose-dependent radiosialadenitis. After a dose of 16 Gy an intra- and extra-cellular oedema developed in the salivary glands. Progressive vacuolisation (30 Gy) developed into lipomatosis (46 Gy) and necrotic changes (60 Gy) in the parotid glands. Six months after irradiation treatment, the chronic histomorphological damages corresponded to stage II according to Seifert. The corresponding loss in gland function investigated by measurement of the 99mTc-pertechnetate uptake of the salivary glands was 13% (16 Gy), 26% (30 Gy), 57% (46 Gy), 75% (60 Gy) and 66.5% (6 months post-irradiation). The presented animal model is suitable to demonstrate the correlation of histomorphological and sialoscintigraphical findings.

Topics: Animals; Cobalt Radioisotopes; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Gamma Rays; Head and Neck Neoplasms; Male; Radiation Injuries; Radiation Tolerance; Radionuclide Imaging; Radiotherapy, Adjuvant; Rats; Salivary Glands; Sialadenitis; Sodium Pertechnetate Tc 99m; Xerostomia

The use of antibodies as targeting agents for the delivery of radioisotopes to tumors is a promising concept that has received widespread attention since the advent of monoclonal antibody (mAb) technology. The following studies are described in this article: the 99mTc-randiolabeling of 2-iminothiolane (2-IT) modified antibodies and 6-p-isothiocyanatobenzyl- diethylene-triamine penta-acetic acid (CITC-DTPA) immunoconjugates of anti-EGF-receptor antibodies murine ior egf/r3 and humanized h-R3; the analytical methods for quality control of the radiopharmaceutical such as instant thin layer chromatography-silica gel (ITLC-SG); the biological assessment of the radiolabeled molecule using flow cytometry analysis; in vitro stability studies with cysteine and DTPA challenge and the biodistribution studies in 4NMRI xenografted nude mice with U-87 human glioblastoma multiforme and MDA-MB-468 breast cancer cell lines. Labeling efficency of (96.48 +/- 0.70%) (98.42 +/- 0.38%), (94.8 +/- 1.25%) and (96.41 +/- 0.89%) was achieved for 99mTC-2-IT ior efg/r3, 99mTc-CITC-DTPA- ior egf/r3, 99mTc-CITC-DTPA- h-R3 and 99mTc-DIACIM h-R3, respectively. Radiocolloids were less than 2.0% in all cases. The biological activity measured by flow cytometry analysis using the MDA-MB-468 breast cancer cell line showed an immunoreactivity fraction greater than 85% in all concentrations of each immunoconjugate. Challenge studies demonstrated no evidence of transcomplexation of 99mTc to 1.0 mM DTPA for 2-IT modified antibody ior egf/r3 and CITC-DTPA immunoconjugates and only 8.7%, 4.9% and 5.0% of the 99mTc-radiolabeled was transcomplexed to 1.0 mM cysteine after 1 h incubation at 37 degrees C for 2-IT modified antibody ior egf/r3, CITC-DTPA ior egf/r3 and CITC-DTPA h-R3, respectively. Biodistribution studies with 2-IT modified antibodies and CITC-DTPA immunoconjugates indicated high tumor uptake in both cell lines with both immunoconjugates and no accumulation of the radiolabeled antibodies in normal organs.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Central Nervous System Neoplasms; Colonic Neoplasms; Cross-Linking Reagents; Disease Models, Animal; ErbB Receptors; Glioblastoma; Humans; Imidoesters; Immunoconjugates; Immunoglobulin G; Immunoradiometric Assay; Isothiocyanates; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pentetic Acid; Sodium Pertechnetate Tc 99m; Tissue Distribution; Tumor Cells, Cultured

A quick and reproducible method for radiolabeling of Photosan-3(R), a photosensitizer used worldwide for photodynamic therapy (PDT) of cancer, with radioisotope of technetium ((99m)Tc) was developed. The radiotracer was evaluated for radiochemical purity, stability, and finally tissue distribution in a murine tumor model. The (99m)Tc-Photosan-3 prepared by using (99m)Tc-pertechnetate in place of reduced (99m)Tc demonstrated better labeling efficiency (>90%) and reproducibility. The procedure also minimized the radiation exposure to the radiochemist as handling time was considerably reduced. Due to the commercial availability of Photosan-3, the risk of batch-to-batch variation in the in situ synthesis of hematoporphyrin derivative, which is a complex mixture of at least five compounds, was also significantly reduced. The biodistribution studies and tumor scintigraphy confirmed that (99m)Tc-labeled Photosan-3 was preferentially taken up by the neoplastic tissue in a manner similar to the parent compound. In addition to applications in tumor imaging, (99m)Tc-Photosan-3 could also be used for estimating tumor uptake of Photosan-3 as may be required for individualization of clinical protocols of PDT.

Topics: Animals; Carcinoma, Ehrlich Tumor; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Stability; Hematoporphyrins; Metabolic Clearance Rate; Mice; Neoplasm Transplantation; Organ Specificity; Photosensitizing Agents; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sodium Pertechnetate Tc 99m; Technetium; Tin Compounds; Tissue Distribution

Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model.. Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically.. Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals.. Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.

Topics: Amifostine; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Iodine Radioisotopes; Male; Rabbits; Radiation-Protective Agents; Radiobiology; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Salivary Glands; Sodium Pertechnetate Tc 99m

Amlodipine improves exercise capacity in patients with chronic congestive heart failure (HF), but the mechanisms of this effect are unknown.. To test the hypothesis, in a canine model of acute, ischemic HF, that amlodipine increases vascular capacitance and reduces cardiac filling pressures.. Amlodipine was given to 13 anesthetized, splenectomized dogs (six controls and seven with HF). Aortic, left ventricular end-diastolic (LVEDP) and portal venous (Pportal) pressures, cardiac output, portal flow (ultrasonic probe) and intestinal blood volume (IBV, 99mTc blood-pool scintigraphy) were measured. Intestinal vascular conductance (= 1/resistance) and vascular capacitance (CAP) were measured before and 15 mins after repetitive 150 micrograms/kg dosages of amlodipine (maximum cumulative dosage, 1000 micrograms/kg). Pportal-IBV curves were obtained by impeding portal flow (pneumatic cuff), and change in CAP was defined by the change in IBV at Pportal = 7.5 mmHg. HF was induced by microsphere embolization of the left coronary artery.. CAP increased in the control group (+ 28%, P < 0.01) but decreased (-9%, P < 0.05) in the HF group. Left ventricular stroke work increased in the control group (P < 0.05), while it decreased (P < 0.05) in the HF group, suggesting a negative inotropic effect. In the control group, LVEDP increased after amlodipine was given (P < 0.05) but did not change significantly in the HF group.. In the acute experimental HF model, amlodipine failed to increase intestinal vascular CAP or decrease filling pressures, and may have had a negative inotropic effect. The experiment failed to demonstrate a beneficial hemodynamic effect of amlodipine in acute HF, and the mechanism of benefit of this agent in chronic HF remains unclear.

Topics: Acute Disease; Amlodipine; Analysis of Variance; Animals; Calcium Channel Blockers; Cardiovascular System; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Heart Failure; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Time Factors; Vascular Capacitance; Vascular Resistance

Arthritis develops in DBA/1xB10A(4R) mice and Wistar rats upon intraplantar injection of potassium peroxochromate (K3CrO8), and is here quantified by whole blood chemiluminescence (CL) and 99mpertechnetate-imaging (99mTcO4-), and related to overt disease symptoms (the arthritis index). During the aqueous decay of K3CrO8 to chromate (VI), the chromium(V)-bound oxygen is released as superoxide, hydroxyl radicals, singlet oxygen and hydrogen peroxide, the same reactants, which are produced by activated phagocytes during inflammation. Reactive oxygen species (ROS) trigger the breakdown of the sulfhydryl-dependent antioxidant defence system and induce the nuclear factor kappa B-dependent expression of pro-inflammatory cytokines, which prime phagocytic NADPH oxidases to the enhanced production of ROS. During both the acute inflammatory response and the onset of the secondary response in non-injected paws, the phorbolester-stimulated ROS production of phagocytes was significantly enhanced (p < 0.001) and correlated well to the arthritis index (r = 0.797) and the uptake of 99mTcO4- into inflamed joints. Chromate(VI), formed during the decay of K3CrO8, contributes to the progression of arthritis by inhibition of glutathione reductase, thereby increasing intracellular H2O2 concentrations. In addition, Cr(VI) reduced to Cr(V) by ascorbate, catalyzes hydroxyl radical production in the presence of hydrogen peroxide. A stable loop forms, in which ROS, continuously produced by Cr(VI)/Cr(V) redox-cycling, drive the primary response into chronic self-perpetuating inflammation. We see the main application of K3CrO8-induced arthritis and its assessment by both 99mTcO4- imaging and chemiluminescent immunosensoring of phagocytic activity in unseparated blood as for the rapid screening of novel anti-rheumatic drugs and treatments.

Topics: Animals; Arthritis; Chromates; Disease Models, Animal; Luminescent Measurements; Male; Mice; Mice, Inbred DBA; Peroxides; Phagocytosis; Radionuclide Imaging; Rats; Rats, Wistar; Sodium Pertechnetate Tc 99m

With the increasing application of certain surgical procedures to 'day surgery' cases, there has been greater utilization of local anaesthetic agents. Such procedures are undertaken using single infiltration dosage recommendations for lignocaine, both with and without adrenaline. The present paper describes results obtained from a sheep model that considers the role of the regional blood flow of the injected site as a determinant of lignocaine absorption and resultant pharmacokinetics. The peak concentration of lignocaine in plasma following administration to two selected sites of different vascularity (as determined by a technetium99 washout method), as well as the effect of concomitant adrenaline administration, was shown to correlate with the regional blood flow to the site (rs = 0.73, P = 0.008). Extrapolating these animal data to the clinical situation suggests that larger dosages of lignocaine could be used safely for infiltration anaesthesia in regions of poor regional blood flow without posing a threat of lignocaine-induced toxicity, and that the current dosage recommendations could be modified in respect of the regional blood flow of the particular site to be infiltrated.

Topics: Absorption; Animals; Disease Models, Animal; Epinephrine; Forelimb; Half-Life; Hindlimb; Injections, Intramuscular; Injections, Intravenous; Lidocaine; Muscles; Regional Blood Flow; Sheep; Sodium Pertechnetate Tc 99m

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cats; Disease Models, Animal; Escherichia coli Infections; Extravascular Lung Water; Gamma Cameras; Indium; Indium Radioisotopes; Lung; Microcirculation; Organ Size; Proteins; Radioisotope Dilution Technique; Radionuclide Imaging; Shock, Septic; Sodium Pertechnetate Tc 99m; Transferrin

The benefits of inhaled therapy in ventilated neonates are recognized, but the reliability of drug delivery in nebulizer-ventilator circuits is uncertain. We quantified the effect of changing variables. Twenty-three freshly killed rabbits (1.15-1.9 kg) were ventilated via a tracheostomy by a pressure-limited, time-cycled ventilator (Neovent). A radioaerosol of 99Tcm pertechnetate from an Ultravent nebulizer (Mallinkrodt) was fed into the proximal ventilator tubing. Two 3-minute nebulizations at "standard settings" were followed by 2 at altered pressure, frequency, gas flow, I:E ratio, or position of the nebulizer in the circuit. Each nebulization was followed by a 3-minute gamma camera image and total deposited radioactivity was measured in excised lungs and trachea. Images demonstrated good peripheral aerosol deposition. At standard settings, lung deposition averaged 2.8% of the aerosol released. This was decreased markedly by reducing tidal volume (ventilator pressures) and residence time of aerosol (I:E ratio). Reduced gas flow decreased deposition slightly, presumably by increased particle size and marginally reduced tidal volume. Deposition did not change with increased frequency; increased minute ventilation was offset by decreased residence time of the aerosol. We conclude that the Ultravent nebulizer can be used to nebulize drugs in a standard neonatal circuit, although the dose delivered is small. Tidal volume and aerosol residence time are important determinants of aerosol delivery.

Topics: Animals; Bronchopulmonary Dysplasia; Disease Models, Animal; Humans; Infant, Newborn; Lung; Lung Compliance; Lung Diseases; Nebulizers and Vaporizers; Plethysmography; Rabbits; Radionuclide Imaging; Respiration, Artificial; Sodium Pertechnetate Tc 99m; Tidal Volume

To determine the validity of a method for induction of experimental hemarthrosis in dogs and for the nuclear imaging of hemarthrosis, serial technetium-99m pyrophosphate [( 99mTc]PYP) flow and blood-pool scans were performed monthly in eight dogs who received bi-weekly injections of autologous blood into their femoro-tibial joints (also called stifle joint). In four control dogs, one joint was injected with saline while the other joint received only a sham injection. In addition, two dogs received intra-articular injections of autologous blood into their right stifle joint and saline into their left stifle joint. These dogs were studied with 99mTcO4 joint scintigraphy at monthly intervals. The dogs were periodically taken out of the study and explored surgically. Pathologic examination of synovial tissue was performed. Serial radiographs were also obtained and correlated with the scan and surgical findings. There was a striking abnormal increase in blood-pool activity of [99mTc]PYP in the treated stifle joints, commencing at the first examination after 1 mo of blood injections and continuing for the length of the study. All radiographs showed only minimal joint space widening and some soft-tissue swelling. On pathologic examination, both grossly and microscopically, there was profuse pannus formation, with intense inflammatory infiltrate replacing much of the subsynovial fat. The scintigraphic findings correlated well with these pathologic findings. This study not only validates this method for simulating hemophilic hemarthrosis but also suggests that [99mTc]PYP joint scintigraphy is a simple, and noninvasive method for monitoring the early changes in hemophilic arthropathy and is superior to pertechnetate imaging for this disease process. Instead of the previously recommended delayed bone images, we recommend, in addition, flow studies to assess joint hypervascularity and immediate static images to visualize the synovium and joint capsule.

Topics: Animals; Blood; Diphosphates; Disease Models, Animal; Dogs; Hemarthrosis; Hindlimb; Injections, Intra-Articular; Joints; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Pyrophosphate

The induction of global cerebral ischaemia in laboratory animals is difficult to accomplish and has been even more difficult to verify. Most reported verification methods suffer from lack of sensitivity or from being traumatic and highly invasive. We describe a non-traumatic global cerebral ischaemia verification technique which is quantitative, simple, and highly sensitive. Radioactive technetium-99m pertechnetate is injected intravenously during the ischaemic phase of an experiment and the appearance of radioactivity within the animal's head is quantitated using a gamma camera and nuclear medicine computer. Radioactivity levels below the visual perception threshold are readily measured, thus providing a high degree of confidence in assessing the partial or total nature of cerebral ischaemia.

Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Computers; Disease Models, Animal; Radionuclide Imaging; Rats; Scintillation Counting; Sodium Pertechnetate Tc 99m

An animal model of arthritis in the rabbit was employed to assess the radioactivity contribution of joint tissues to externally monitored scintigram positivity. Bone contained the greatest total amount of radioactivity whether the imaging agent was technetium pertechnetate or pyrophosphate, although the greatest percent increase in the arthritis joints over control joints was seen in synovium. Mid-shaft bone in the same region as the arthritic joint also showed increased radioactivity compared with control.

Topics: Animals; Arthritis; Diphosphates; Disease Models, Animal; Evaluation Studies as Topic; Femur; Injections, Intra-Articular; Knee Joint; Rabbits; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Synovial Fluid; Synovial Membrane; Technetium; Technetium Tc 99m Pyrophosphate; Tissue Distribution

A canine model simulating Meckel's diverticulum was used to evaluate the effects of pentagastrin, glucagon, and a combination of the two hormones on the gastrointestinal localization of 99mTc. Pentagastrin produced accelerated uptake of the radionuclide in both the stomach and the ectopic gastric mucosa but resulted in early visualization of the duodenum and a "washout" effect on the radioisotope within the Meckel's diverticulum. Glucagon provided prolonged retention of the radionuclide in the stomach and ectopic mucosa and prevented duodenal visualization. A combination of both hormones produced increased activity in the stomach and experimental Meckel's and decreased duodenal filling. This enhanced target to background contrast and provided improved visualization of the ectopic gastric mucosa.

Topics: Animals; Disease Models, Animal; Dogs; Gastric Mucosa; Glucagon; Meckel Diverticulum; Pentagastrin; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium