technetium-tc-99m-exametazime and Disease-Models--Animal

The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE.. C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [. Significantly reduced perfusion values and significantly enhanced [

Topics: Animals; Brain; Disease Models, Animal; Fluorodeoxyglucose F18; Glucose; Iodine Radioisotopes; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Multimodal Imaging; Neuroimaging; Nuclear Medicine; Positron-Emission Tomography; Radioactive Tracers; Radionuclide Imaging; Sepsis-Associated Encephalopathy; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSC

Topics: Adipocytes; Adipose Tissue; Animals; Cell Differentiation; Cerebrum; Disease Models, Animal; Fibroblast Growth Factor 1; Gene Expression; Humans; Infarction, Middle Cerebral Artery; Infusions, Intravenous; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Radiopharmaceuticals; Rats; Rats, Wistar; Recovery of Function; Rotarod Performance Test; Stroke; Technetium Tc 99m Exametazime; Transgenes

Inhaled hydrogen gas (H2) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of Tc-hexamethylpropyleneamineoxime (HMPAO) and Tc-duramycin to track the effectiveness of H2 therapy in vivo in the hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O2 + 2% N2 (hyperoxia) or 98% O2 + 2% H2 (hyperoxia+H2) for up to 60 h. In vivo scintigraphy images were acquired following injection of Tc-HMPAO or Tc-duramycin. For hyperoxia rats, Tc-HMPAO and Tc-duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 h, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxia+H2 rats. Hyperoxia exposure increased glutathione content in lung homogenate (36%) more than hyperoxia+H2 (21%), consistent with increases measured in Tc-HMPAO lung uptake. In 60-h hyperoxia rats, pleural effusion, which was undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue 3-nitrotyrosine expression increased by 790%. Increases were reduced by 69% and 59%, respectively, in 60-h hyperoxia+H2 rats. This study detects and tracks the anti-oxidant and anti-apoptotic properties of H2 therapy in vivo after as early as 24 h of hyperoxia exposure. The results suggest the potential utility of these SPECT biomarkers for in vivo assessment of key cellular pathways in the pathogenesis of ALI and for monitoring responses to therapies.

Topics: Acute Lung Injury; Administration, Inhalation; Animals; Bacteriocins; Disease Models, Animal; Hydrogen; Hyperoxia; Male; Molecular Imaging; Organotechnetium Compounds; Rats; Technetium Tc 99m Exametazime

Cerebral ischemia is a leading cause of disability worldwide and no other effective therapy has been validated to date than intravenous thrombolysis. In this context, many preclinical models have been developed and recent advances in preclinical imaging represent promising tools. Thus, we proposed here to characterize in vivo time profiles of cerebral blood flow, blood-brain barrier disruption and apoptosis following a transient middle cerebral artery occlusion in rats using SPECT/CT imaging.. Rats underwent a 1-h middle cerebral artery occlusion followed by reperfusion. Cerebral blood flow, blood-brain barrier disruption and apoptosis were evaluated by SPECT/CT imaging using respectively (99m)Tc-HMPAO, (99m)Tc-DTPA and the experimental (99m)Tc-Annexin V-128, up to 14 days after middle cerebral artery occlusion. Histological evaluation of apoptosis has been performed using TUNEL method to validate the (99m)Tc-Annexin V-128 uptake.. (99m)Tc-HMPAO cerebral blood flow evaluation showed hypoperfusion during occlusion, partially restored on days 4 and 7 and sustained up to 14 days after middle cerebral artery occlusion. (99m)Tc-DTPA SPECT/CT showed a blood-brain barrier disruption starting on day 1 post-middle cerebral artery occlusion, peaking on day 2, with barrier integrity totally restored on day 7. (99m)Tc-Annexin V-128 SPECT/CT imaging showed significant positive correlation with TUNEL immunohistochemistry and allowed ischemic-induced apoptosis to be detected from day 2 to day 7, peaking on day 3 after middle cerebral artery occlusion.. Using SPECT/CT imaging, we showed that after transient middle cerebral artery occlusion in rat there was a sustained decrease in cerebral blood flow followed by blood-brain barrier disruption preceding meanwhile apoptosis. Rodent SPECT/CT imaging of cerebral blood flow, blood-brain barrier disruption and apoptosis appears to be an efficient tool for evaluating neuroprotective drugs and regenerative therapies against cerebral ischemia and time-windows for therapeutic intervention.

Topics: Animals; Apoptosis; Blood-Brain Barrier; Brain; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Disease Progression; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Male; Multimodal Imaging; Pentetic Acid; Radiopharmaceuticals; Rats, Sprague-Dawley; Technetium Tc 99m Exametazime; Time; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The development of clinically relevant preclinical models that mimic the hallmarks of neurodegenerative disease is an ongoing pursuit in early drug development. In particular, robust physiological characterization of central nervous system (CNS) disease models is necessary to predict drug delivery to target tissues and to correctly interpret pharmacodynamic responses to disease-modifying therapeutic candidates. Efficient drug delivery across the blood-CNS barrier is a particularly daunting task, prompting our strategy to evaluate the biodistribution of five distinct molecular probes in a well-characterized mouse model of neurodegeneration. A transgenic mouse model of amyotrophic lateral sclerosis was selected based on a phenotype resembling clinical symptoms, including loss of motor neurons from the spinal cord and paralysis in one or more limbs, due to expression of a G93A mutant form of human superoxide dismutase (SOD1). The tissue distributions of two proteins, albumin and a representative immunoglobulin G antibody, as well as two blood flow markers, the lipophilic blood flow marker Ceretec (i.e., (99m)Tc-HMPAO) and the polar ionic tracer, rubidium-86 chloride ((86)RbCl), were measured following intravenous injection in SOD1(G93A) and age-matched control mice. The radiopharmaceutical TechneScan PYP was also used to measure the distribution of (99m)Tc-labeled red blood cells as a blood pool marker. Both the antibody and (86)Rb were able to cross the blood-spinal cord barrier in SOD1(G93A) mice to a greater extent than in control mice. Although the biodistribution patterns of antibody, albumin, and RBCs were largely similar, notable differences were detected in muscle and skin. Moreover, vastly different biodistribution patterns were observed for a lipophilic and polar perfusion agent, with SOD1(G93A) mutation resulting in reduced renal filtration rates for the former but not the latter. Overall, the multiprobe strategy provided an opportunity to efficiently collect an abundance of physiological information, including the degree and regional extent of blood-CNS barrier permeability, in a preclinical model of neurodegeneration.

Topics: Amyotrophic Lateral Sclerosis; Animals; Blood Volume; Blood-Brain Barrier; Cerebrovascular Circulation; Chlorides; Disease Models, Animal; Drug Delivery Systems; Female; Humans; Immunoglobulin G; Mice; Mice, Mutant Strains; Mice, Transgenic; Nerve Degeneration; Protein Transport; Radionuclide Imaging; Radiopharmaceuticals; Rubidium; Rubidium Radioisotopes; Superoxide Dismutase; Technetium Tc 99m Exametazime; Tissue Distribution

Arterial spin labelling (ASL) is increasingly available for noninvasive cerebral blood flow (CBF) measurement in stroke research. Here, a pseudo-continuous ASL technique (pCASL) was evaluated against (99m)Tc-D, L-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) autoradiography in a rat stroke model. The (99m)Tc-HMPAO was injected (intravenously, 225 MBq) during pCASL acquisition. The pCASL and (99m)Tc-HMPAO autoradiography CBF measures, relative to the contralateral hemisphere, were in good agreement across the spectrum of flow values in normal and ischemic tissues. The pCASL-derived quantitative regional CBF values (contralateral: 157 to 177 mL/100 g per minute; ipsilateral: 9 to 104 mL/100 g per minute) were consistent with the literature values. The data show the potential utility of pCASL for CBF assessment in a rat stroke model.

Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Magnetic Resonance Angiography; Radiography; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Spin Labels; Stroke; Technetium Tc 99m Exametazime

Blood flow interruption in a cerebral artery causes brain ischemia and induces dramatic changes of perfusion and metabolism in the corresponding territory. We performed in parallel positron emission tomography (PET) with [(15)O]H(2)O, single photon emission computed tomography (SPECT) with [(99m)Tc]hexamethylpropylene-amino-oxime ([(99m)Tc]HMPAO) and ultrasonic ultrafast shear wave imaging (SWI) during, immediately after, and 1, 2, 4, and 7 days after middle cerebral artery occlusion (MCAO) in rats. Positron emission tomography and SPECT showed initial hypoperfusion followed by recovery at immediate reperfusion, hypoperfusion at day 1, and hyperperfusion at days 4 to 7. Hyperperfusion interested the whole brain, including nonischemic areas. Immunohistochemical analysis indicated active angiogenesis at days 2 to 7, strongly suggestive that hyperperfusion was supported by an increase in microvessel density in both brain hemispheres after ischemia. The SWI detected elastic changes of cerebral tissue in the ischemic area as early as day 1 after MCAO appearing as a softening of cerebral tissue whose local internal elasticity decreased continuously from day 1 to 7. Taken together, these results suggest that hyperperfusion after cerebral ischemia is due to formation of neovessels, and indicate that brain softening is an early and continuous process. The SWI is a promising novel imaging method for monitoring the evolution of cerebral ischemia over time in animals.

Topics: Animals; Cerebrovascular Circulation; Disease Models, Animal; Elasticity; Elasticity Imaging Techniques; Male; Neovascularization, Physiologic; Perfusion; Positron-Emission Tomography; Rats; Rats, Sprague-Dawley; Stroke; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

Topics: Animals; Disease Models, Animal; Electron Transport Complex I; Electron Transport Complex IV; Glutathione; Hyperoxia; Injections, Intravenous; Lung; Lung Injury; Malates; Male; Mitochondria; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Technetium Tc 99m Exametazime

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas (99m)Tc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury.. Male Sprague-Dawley rats were preexposed to either normoxia (21% O(2)) or hyperoxia (85% O(2)) for up to 21 d. For imaging, the rats were anesthetized and injected intravenously with either (99m)Tc-HMPAO or (99m)Tc-duramycin (both 37-74 MBq), and planar images were acquired using a high-sensitivity modular γ-camera. Subsequently, (99m)Tc-macroagreggated albumin (37 MBq, diameter 10-40 μm) was injected intravenously, imaged, and used to define a lung region of interest. The lung-to-background ratio was used as a measure of lung uptake.. Hyperoxia exposure resulted in a 74% increase in (99m)Tc-HMPAO lung uptake, which peaked at 7 d and persisted for the 21 d of exposure. (99m)Tc-duramycin lung uptake was also maximal at 7 d of exposure but decreased to near control levels by 21 d. The sustained elevation of (99m)Tc-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 d.. These results suggest the potential use of (99m)Tc-HMPAO and (99m)Tc-duramycin as redox and cell-death imaging biomarkers, respectively, for the in vivo identification and assessment of different stages of lung injury.

Topics: Animals; Bacteriocins; Biological Transport; Chronic Disease; Disease Models, Animal; Hyperoxia; Lung; Male; Oxidative Stress; Peptides; Radionuclide Imaging; Rats; Rats, Sprague-Dawley; Technetium Tc 99m Exametazime

Evaluating the efficacy of therapy in experimental inflammatory bowel disease (IBD) requires information about inflammatory activity in bowel segments or leukocyte recruitment and about kinetics in the follow-up of treatment. This study evaluated a noninvasive scintigraphic technique able to assess neutrophil trafficking in a mouse model of dextran sulfate sodium (DSS)-induced colitis.. Groups of 4 BALB/c mice were assessed at baseline and after 1, 3, 5, and 8 d of treatment with DSS. Donor neutrophils were harvested by rinsing of the peritoneal cavity with phosphate-buffered saline 5 h after intraperitoneal injection of proteose peptone contained in phosphate-buffered saline and labeled with freshly prepared (99m)Tc-hexamethylpropylene amine oxime (HMPAO). Pinhole SPECT of the abdomen was performed 1 h after reinjection of 50 MBq of labeled neutrophils. In addition, the severity of inflammation was determined by histologic examination. The possibilities of the technique were illustrated by scintigraphic assessment of neutrophil trafficking with and without blocking of neutrophil migration by a CD97 monoclonal antibody in mice with DSS-induced colitis.. Colonic uptake of (99m)Tc-HMPAO neutrophils was determined with dedicated animal pinhole SPECT in mice with DSS-induced colitis and correlated well with histologic findings (R = 0.81) and wet colon weight (R = 0.87) and moderately with clinical weight loss (R = 0.62). The neutrophil uptake ratio was reduced significantly (P < 0.01) by blocking of neutrophil migration capacity with the CD97 antibody.. Animal pinhole SPECT can be used to study inflammatory activity and neutrophil recruitment in vivo in experimental colitis.

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Neutrophils; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.

Topics: Animals; Blood Platelets; Coronary Disease; Disease Models, Animal; Hemostatics; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Necrosis; P-Selectin; Platelet Activation; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Swine; Technetium Tc 99m Exametazime; Thrombin

Port-site recurrences have delayed the uptake of laparoscopic colectomy, but the etiology of these is incompletely understood. These studies were designed to investigate variables such as the size of the tumor inoculum and the volume and pressure of the insufflated gas during operative laparoscopy that might affect the deposition of these cells in relation to trocars and port sites.. Radiolabeled human colon cancer cells were injected into the peritoneal cavity of pigs. Three trocars were inserted, and the abdomen was insufflated with carbon dioxide. The movement of cells within the abdomen was traced on a gamma camera. After 2 h, the trocars were removed and the port sites excised. Two studies were performed. In the first study, tumor inocula were varied from 1.5 x 10(5) to 120 x 10(5). In the second study, insufflation pressure was varied, with pressures 0, 4, 8 and 12 mmHg were studied.. When larger tumor inocula were injected, the contamination of both trocars (p = 0.005, Kendall's rank correlation) and trocar sites (p = 0.04, Kendall's rank correlation) increased. The deposition of cells on a trocar site was linked to contamination of its trocar (p = 0.03, chi-square), but the contamination of trocars did not always result in trocar-site contamination (p = 0.5, chi-square). Increased volumes of gas insufflation caused increased intraabdominal movement of tumour cells (p = 0.01, Kendall's rank correlation), although this did not lead to greater contamination of trocars or port sites (p = 0.82, Kendall's rank correlation). Decreased insufflation pressures resulted in increased contamination of trocars and port sites (p = 0.01, Kendall's rank correlation).. If clinical situations parallel this study, strategies such as increasing insufflation pressure, reducing episodes of desufflation and gas leaks, and using frequent intraabdominal lavage may help to reduce the numbers of viable tumor cells displaced to port sites during laparoscopic surgery for intraabdominal malignancy. This may reduce the rate of port-site metastases.

Topics: Abdominal Wall; Animals; Carbon Dioxide; Catheterization; Cell Survival; Colonic Neoplasms; Disease Models, Animal; Equipment Contamination; Female; Humans; Injections, Intraperitoneal; Insufflation; Laparoscopy; Neoplasm Seeding; Pelvis; Peritoneal Cavity; Pressure; Radionuclide Imaging; Surgical Instruments; Swine; Technetium Tc 99m Exametazime; Tumor Cells, Cultured

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

Topics: Animals; Autoradiography; Cell Hypoxia; Cerebrovascular Circulation; Cerebrovascular Disorders; Diffusion; Disease Models, Animal; Magnetic Resonance Imaging; Male; Nitroimidazoles; Rats; Rats, Wistar; Technetium Tc 99m Exametazime

We developed a new method to quantitate leukocyte accumulation in tissues and used it to examine the time course and severity of acute experimental pancreatitis.. Leukocyte activation and infiltration are believed to be critical steps in the progression from mild to severe pancreatitis and responsible for many of its systemic complications.. Pancreatitis of graded severity was induced in Sprague-Dawley rats with a combination of caerulein and controlled intraductal infusion. Technetium-99m (99mTc)-labeled leukocytes were quantified in pancreas, lung, liver, spleen, and kidney and compared with myeloperoxidase activity. The severity of pancreatitis was ascertained by wet/dry weight ratio, plasma amylase, and trypsinogen activation peptide in the pancreas. The time course of leukocyte accumulation was determined over 24 hours.. Pancreatic leukocyte infiltration correlated well with tissue myeloperoxidase concentrations. In mild pancreatitis, leukocytes accumulated only in the pancreas. Moderate and severe pancreatitis were characterized by much greater leukocyte infiltration in the pancreas than in mild disease (p < 0.01), and increased 99mTc radioactivity was detectable in the lung as early as 3 hours. 99mTc radioactivity correlated directly with the three levels of pancreatitis.. Mild pancreatitis is characterized by low-level leukocyte activation and accumulation in the pancreas without recruitment of other organs; marked leukocyte accumulation was found in the pancreas and in the lung in more severe grades of pancreatitis. These findings provide a basis for the pathophysiologic production of cytokines and oxygen free radicals, which potentiate organ injury in severe pancreatitis. This study validates a new tool to study local and systemic effects of leukocytes in pancreatitis as well as new therapeutic hypotheses.

Topics: Acute Disease; Animals; Ceruletide; Disease Models, Animal; Disease Progression; Gastrointestinal Agents; Leukocytes; Male; Pancreatitis; Radiopharmaceuticals; Random Allocation; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Severity of Illness Index; Technetium Tc 99m Exametazime

In this study, liposomes labeled with 99mTc have been evaluated as tumor imaging agents.. Liposomes containing reduced glutathione and carrying either a negative surface charge or no surface charge were labeled with 99mTc using the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO). The 99mTc-liposomes were intravenously injected into the tail vein of nuce mice which had been implanted intramuscularly in the thigh with nontransfected Chinese hamster ovary cells. Gamma camera images were acquired at 1, 4 and 22 hr and compared with tissue biodistribution studies at 24 hr postinjection.. Tumors could be distinguished from normal thigh muscle at 4 hr postinjection for both formulations. Tumor-to-muscle ratios were not significantly different for the two formulations due to the increased normal muscle activity at 24 hr for the neutral liposomes. Liver-to-tumor, liver-to-blood, spleen-to-tumor and spleen-to-blood ratios were significantly lower for the neutral 99mTc-liposomes than for the negative 99mTc-liposomes. Neutral 99mTc-liposomes were cleared slower by the reticuloendothelial system, and therefore remained in the circulation for a longer period of time.. The results of this study indicate that both formulations could be used as tumor imaging agents, but that neutral 99mTc-liposomes would be more suitable as a drug delivery agent due to their increased total uptake by the tumor and decreased nonspecific uptake by the reticuloendothelial system.

Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Disease Models, Animal; Female; Liposomes; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime; Tissue Distribution

Selective uptake of the cerebral blood-flow imaging agent 99mTc-hexamethylpropyleneamine oxime (HM-PAO) by Human Herpesvirus 1 (HSV-1) infected cells was investigated in vivo and in vitro. No specific uptake of HM-PAO was observed either in encephalitic rats (by brain scintigraphic imaging or by immunoperoxidase staining/autoradiography of brain sections) or in HSV-1 infected Vero cells.

Topics: Animals; Antiviral Agents; Autoradiography; Brain; Disease Models, Animal; Encephalitis; Female; Herpesviridae Infections; Humans; Immunoenzyme Techniques; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Rats; Rats, Inbred Strains; Simplexvirus; Technetium Tc 99m Exametazime; Vero Cells