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PubMed1992

[Diagnostic value of planar perfusion scintigraphy of the heart using Technetium Tc 99m with methoxy-isobutylisonitrile (MIBI)].

99mTc-MIBI (2 methoxy -isobutylisonitrile) belongs to the new generation of radiopharmaceuticals used for studies of myocardial perfusion. Particularly convenient characteristics of the compound prompted numerous studies of its usefulness for scintigraphic diagnostics of coronary artery disease and myocardial heart infarct (detection, localization, size). In the present paper the diagnostic utility of planar heart scintigraphy with 99mTc MIBI is assessed, the compound had been prepared in the Department of Nuclear Medicine, Medical University of Lódź. The scope of the study included detection of stress induced ischaemia and of permanent perfusion defects, treated as post infarct scars in myocardium. The study was made on 109 patients (78 males, 31 females; age 32-68 years). The first group comprised 56 patients with suspected or diagnosed coronary artery disease, however, without history of previous heart infarct. Results of stress and rest scintigraphy were juxtaposed with those of coronarography, which served as a reference method. In 25 patients the latter revealed critical (greater than 70%) stricture of 1 or 2 coronary arteries. In 31 patients of this group the vessels were either of normal appearance or only marginally stricture. Sensitivity, specificity and accuracy of the scintigraphy in diagnosis of ischaemia due to critical narrowing of coronary arteries amounted to 80, 84 and 82 per cent, respectively. Localisation of perfusion defects was adequate in 20 out of 31 vessels (64 per cent). The second group of patients included 53 individuals with previous heart infarct (25 and 11 had a transmural and nontransmural infarct of the anterior wall, respectively; in 12 and 5 a transmural and nontransmural infarct of the inferior wall was diagnosed, accordingly).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Renal cortical perfusion--preliminary experience with the dynamic spatial reconstructor (DSR).

The three-dimensional image data generated by the Dynamic Spatial Reconstructor (DSR) enables measurement of the three-dimensional distribution of blood supply in organs. We have applied this imaging technique to evaluate renal cortical blood flow distribution and compare it with distribution of radiolabeled microspheres. The DSR, a high temporal resolution volumetric roentgenographic computed tomographic scanner, was used to scan the volume containing a kidney in 0.13-0.26 s and repeating this scan 8-4 times per s for six s during a renal arteriogram. Five anesthetized dogs were studied in the prone position with the left kidney exteriorized through a flank incision. An electromagnetic flowmeter was placed around the renal artery and a needle placed retrograde into the artery for injection of a 2 cc bolus of contrast agent. During the scan the contrast agent was injected over a four s period during which radioactively labelled microspheres were injected into the left atrium. The tomographic images of approximately 10 parallel, 5 mm thick sagittal slices corresponding to the slices of the kidney used for counting microspheres in the cortical layers were displayed and analyzed. The time point chosen for analysis was the one in which peak brightness (i.e., concentration of contrast agent) was detected in the cortex. The spatial distribution of peak brightness values was compared to the number of microspheres at the same sampling locations. The microsphere-based value of regional cortical blood flow fell below the regression line for the juxtamedullary cortex and above for the outer cortex. This result is consistent with the preferential distribution of microspheres to the outer cortex whereas the contrast agent distributed more uniformly throughout the cortex.

Animals↗
PubMed2003

Increased MIBG uptake after transfer of the human norepinephrine transporter gene in rat hepatoma.

UNLABELLED: The transport of MIBG by the human norepinephrine transporter (hNET) seems to be the critical step in the treatment of MIBG-concentrating tumors. Therefore, we investigated whether the accumulation of MIBG may be induced by retroviral transfection of the hNET gene in Morris hepatoma cells. METHODS: A bicistronic retroviral vector for the transfer of the hNET coding sequence and the hygromycin resistance gene was generated. Morris hepatoma cells (MH3924A) were infected with the respective retroviral particles, and hNET-expressing cell lines MHhNEThyg1 to MHhNEThyg9 were obtained through hygromycin selection. The uptake of (3)H-norepinephrine or (131)I-MIBG and the efflux of (131)I-MIBG were determined in transfected and wild-type cells. In addition, the (131)I-MIBG distribution was monitored in nude mice and rats bearing wild-type and hNET-expressing hepatomas. RESULTS: hNET-expressing hepatoma cell lines accumulated up to 36 times more norepinephrine than did wild-type cells and 8 times more than did hNET-expressing neuroblastoma cell line SK-N-SH. The addition of nisoxetine, a selective inhibitor of noradrenaline uptake, inhibited norepinephrine uptake. Maximal (131)I-MIBG accumulation was observed 2 h after incubation and was followed by 43% efflux within 4 h after the (131)I-MIBG-containing medium had been removed. In vivo experiments performed with nude mice bearing both hNET-expressing and wild-type tumors showed a 10-fold-higher accumulation of (131)I-MIBG in transfected tumors than in wild-type tumors. The ex vivo calculations revealed doses of 605 and 75 mGy in hNET-expressing and wild-type tumor tissues, respectively. CONCLUSION: Transduction of the hNET gene enables Morris hepatoma cells to accumulate norepinephrine and MIBG. However, the retention of MIBG is brief; therefore, the absorbed dose of radiation in vivo is not expected to be therapeutically effective.

3-Iodobenzylguanidine↗
PubMed1983

[Autonomy and heterogeneity of the follicle in euthyroid and hyperthyroid human nodular goiter: answer to old riddles?].

The mechanisms responsible for the transformation of a morphologically and functionally normal thyroid into a heterogeneous eu- or hyperthyroid nodular goitre are summarized. The 3 basic processes of goitre pathogenesis are: 1. Each goitre develops from a normal thyroid gland by generation of new follicles. 2. New follicles are formed by multiplication of preferentially replicating cell clones of the follicular epithelium. Follicles already begin multiplying in response to a goitrogenic stimulus too weak to enhance metabolic functions other than replication. 3. The epithelial cells of normal follicles are not homogeneous and monoclonal, but belong to different populations with different metabolic equipment. Therefore, the daughter follicles may be metabolically different, e.g. in iodinating capacity. A certain degree of autonomous, i.e. TSH-dependent function is inborn to all follicles. The individual degree of autonomy of iodine turnover is not variable during goitrogenesis but determined by the metabolic individuality of the mother cell at the moment of folliculoneogenesis. These three basic processes explain the typical heterogeneity of nodular goitre. From autonomous highly iodinating cell families, autonomous "hot" daughter follicles arise which may be scattered all over the gland either as single follicles or as clusters of varying size (so-called "disseminated autonomy"). Particularly large clusters of "hot" follicles result in scintigraphically visible hot nodules, often called "toxic adenomas". Hyperthyroidism appears when the total joint autonomous hormone production of normal and "hot" follicles exceeds the requirements of the organism. The large majority of goitre nodules, including the so-called "toxic adenoma", are not true monoclonal benign neoplasias. Rather, they are built up by the same polyclonal heterogeneous follicles as extranodular goitre tissue. They have no choice but to expand in nodular fashion because they replicate within a poorly extensible network of connective tissue. This network of fibrous tissue results from scarring of multiple hemorrhagic necrosis occurring episodically during goitre growth.

Adult↗
PubMed1988

Efficacy of quantitative hepatobiliary scintigraphy and fatty-meal sonography for evaluating patients with suspected partial common duct obstruction.

In this study we evaluated by blinded design the diagnostic efficacy of two noninvasive techniques, quantitative hepatobiliary scintigraphy (QHS) and fatty-meal sonography (FMS), for evaluating patients with suspected partial common duct obstruction. Quantitative hepatobiliary scintigraphy was performed on 56 cholecystectomized individuals (22 asymptomatic controls, 28 patients with suspected partial common duct obstruction, and 6 nonjaundiced cirrhotics) and FMS was done in 51 cases. For QHS, time-activity curves were generated for regions of interest over the liver, hepatic hilum, and common duct. For FMS, we measured common duct diameter before and 45 min after a fatty meal (Lipomul, 1.5 ml/kg). Each of the 28 patients with suspected partial common duct obstruction and 6 cirrhotic patients underwent endoscopic retrograde cholangiography, often accompanied by sphincter of Oddi manometry. Findings from these examinations were taken as the gold standard to determine the presence or absence of conditions that could account for intermittent symptomatic partial common duct obstruction. The most sensitive indicators for a positive test were a 45-min isotope clearance of less than 63% for QHS and a common duct increase of greater than or equal to 2 mm after the fatty meal for FMS. Of 28 patients with suspected partial common duct obstruction, 15 were judged to be true-positive and 13 true-negative. The 6 cirrhotic patients were without common duct obstruction. The study findings showed that each test had a 67% sensitivity that improved to 80% when the findings from both test results were combined. The specificity of QHS was 85% and that of FMS was 100%. All 6 cirrhotic patients had negative findings on FMS and 4 were false-positive on QHS. The true-positives included 8 patients with a small common duct stone and 6 with obstructive sphincter of Oddi dysfunction (4 stenosis, 2 dyskinesia). We conclude that noninvasive QHS and FMS afford good sensitivity and specificity for evaluating cholecystectomized patients with suspected partial common duct obstruction.

Adult↗
PubMed2002

Pharmacokinetics and gamma scintigraphy evaluation of two enteric coated formulations of didanosine in healthy volunteers.

AIMS: The aims of the study were to evaluate the bioavailability of didanosine from the encapsulated enteric coated beads (1 x 200 mg; enteric beads) and enteric coated mini-tablets (4 x 50 mg; enteric tablet) formulations relative to the chewable/dispersible buffered tablets (2 x 100 mg; buffered tablet), and to study their rate of gastrointestinal transit. METHODS: This was a single-dose, randomized, three-way crossover study in 18 healthy male volunteers. A 200 mg dose of didanosine was given in each period and each formulation contained a gamma radiation-emitting isotope. Pharmacokinetic parameters determined were Cmax, tmax, AUC(0, infinity ) and t1/2. Bioequivalence was assessed using the confidence interval (CI) of 0.80, 1.25 for Cmax and AUC(0, infinity ). Scintigraphic images were recorded and gastrointestinal transit profiles were generated. RESULTS: The point estimate and 90% CI of the ratio of Cmax for the enteric beads and enteric tablet relative to the buffered tablet was 0.71 (0.59, 0.85) and 0.55 (0.46, 0.66), respectively. The tmax was significantly different for the enteric beads (median, 1.33 h) and the enteric tablet (median, 2.83 h) than for the buffered tablet (median, 0.67 h). The AUC(0, infinity ) satisfied the bioequivalence criteria, and the point estimate and 90% CI of the ratio were 1.02 (0.91, 1.15) and 0.92 (0.82, 1.04) for the enteric beads and enteric tablet, respectively. The AUC(0, infinity ) values appeared to be less variable with the enteric beads (% CV = 19%) than with the enteric tablet (% CV = 33%). The t1/2 values were not significantly different between formulations, and the mean values ranged from 1.82 to 1.92 h. Inspection of the individual scintigraphy profiles and concentration-time curves suggested that didanosine was absorbed throughout the small intestine. Gastrointestinal transit parameters were higher for both enteric formulations than for the buffered tablet, indicating slower transit of the enteric formulations. Between the enteric formulations, gastric emptying was slower for the enteric beads than for the enteric tablet; however, plasma didanosine concentrations were observed sooner for the enteric beads, suggesting that the enteric coat for the beads dissolved more rapidly. CONCLUSIONS: The enteric beads and enteric tablet formulations of didanosine were equivalent to the buffered tablet in their extent of absorption. Although the gastric emptying of the enteric tablet was faster, based on the rapid uncoating and the lower variability in AUC, the enteric beads were chosen for further clinical development.

Adult↗
PubMed2004

Automated quantification of 99mTc sestamibi myocardial perfusion compared with visual analysis.

OBJECTIVES: The visual interpretation of 99mTc sestamibi single photon emission computed tomography (SPECT) myocardial perfusion images can be challenging due to the quantity of scan information generated, the large number of normal variants, attenuation artifacts and gender differences. The development of automated, computer derived, quantitative indices of perfusion can assist in this interpretation by providing an objective measure. It is important to verify that similar results can be obtained when the software is used in centres outside those where the algorithms were initially developed. Our objective was to assess the degree of concordance between the visual and automated diagnostic assessments of 99mTc sestamibi SPECT. METHODS: We studied 718 patients referred for 99mTc sestamibi SPECT myocardial perfusion imaging. The SPECT studies were initially interpreted visually without benefit of computer based analysis, and were then subjected to blinded reprocessing to extract quantitative indices of perfusion. RESULTS: There was very good agreement between the visual and quantitative diagnostic classifications. When a visual abnormality was taken to be the reference standard, the automated summed stress score (SSS) showed agreement (SSS>3) in 80% (kappa 0.60, P<0.0001). The area under the receiver operating characteristic (ROC) curve was 0.89 (95% confidence interval (CI), 0.86-0.91). Concordance was greater in those with previous myocardial infarction or severe perfusion defects, but was not affected by age, prior revascularization, stress procedure or heart rate. Concordance over the presence or absence of visual reversibility and the summed difference score (SDS) in abnormal scans was slightly lower (overall agreement 73% (kappa 0.36, P<0.00001) and ROC area 0.84 (95% CI, 0.77-0.90)). CONCLUSION: Automated quantification of 99mTc sestamibi SPECT myocardial perfusion with the SSS and SDS provides objective diagnostic information and concordance when compared with conventional visual image interpretation.

Algorithms↗
PubMed2005

Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies.

UNLABELLED: We present a method to measure the regional rate of cellular proliferation using a positron-emitting analog of thymidine (TdR) for human imaging studies. The method is based on the use of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) to estimate the flux of TdR through the exogenous pathway. The model reflects the retention of FLT-monophosphate (FLTMP), which is generated by the phosphorylation of FLT by thymidine kinase 1 (TK1), the initial step in the exogenous pathway. METHODS: A model of FLT kinetics has been designed based on the assumptions of a steady-state synthesis and incorporation of nucleotides into DNA, an equilibration of the free nucleoside in tissue with the plasma level, and the relative rates of FLT and TdR phosphorylation from prior data using direct analysis with in vitro assays. A 2-compartment model with 4 rate constants adequately describes the kinetics of FLT uptake and retention over 120 min and leads to an estimation of the rate of cellular proliferation using the measured FLT blood clearance and the dynamic FLT uptake curve. RESULTS: Noise characteristics of kinetic parameter estimates for 3 tissues were assessed under a range of conditions representative of human cancer patient imaging. The FLT flux in these tissues can be measured with a SE of <5%, and FLT transport can be estimated with a SE of <15%. Abbreviating the data collection to 60 min or neglecting k(4), giving a 3-parameter model, results in an unsatisfactory loss of accuracy in the flux constant in tumor simulations. CONCLUSION: These analyses depict model behavior and provide expected values for the accuracy of parameter estimates from FLT imaging in human patients. Our companion paper describes the performance of the model for human data in patients with lung cancer. Further studies are necessary to determine the fidelity of K(FLT) (FLT flux) as a proxy for K(TDR) (thymidine flux), the gold standard for imaging cellular proliferation.

Algorithms↗
PubMed1999

Technetium-99m-EC and other potential new agents in renal nuclear medicine.

Search for the ideal radiopharmaceutical to measure effective renal plasma flow (ERPF) has been underway since the early 1960s. Although ortho-iodohippuran (OIH) has biological properties suited for measurement of ERPF, the imaging characteristics are less than desirable. With the advent of the molybdenum-99/technetium-99m generators, efforts have focused on the development of a technetium-99m agent to measure ERPF. Over the last 10 to 15 years several promising technetium-99m renal imaging agents have been developed. Early examples of technetium-99m renal agents such as 99mTc-CO2DADS and 99mTc-PAHIDA, although not ideal replacements for OIH, demonstrated that a technetium-99m complex could be actively transported by the renal tubules and provided the impetus for development of new technetium-99m renal agents. The next breakthrough in technetium-99m renal agents was the development of the triamide mercaptide class of chelating agents by Fritzberg et al. To date the most promising compound in this class is mercaptoacetyltriglycine (MAG3). 99mTc-MAG3 is currently the agent of choice, but it is by no means the perfect replacement for OIH. Problems with high plasma protein binding and clearances that are only 50% to 60% of the OIH clearance make measurement of ERPF difficult. The serendipitous discovery that metabolites of the brain agent 99mTc-ethylenedicysteine diethylester (99mTc-L,L-ECD) are rapidly excreted in the urine has led to the evaluation of 99mTc-L,L-ethylenedicysteine (99mTc-L,L-ECD) as a potential renal imaging agent. Studies that have evaluated 99mTc-L,L-EC in animals, normal human volunteers, and patients with various renal disorders reveal that the renal clearance of 99mTc-L,L-EC is higher than 99mTc-MAG3 and more closely approaches that of OIH. Other approaches that are being examined in the development of the ideal renal imaging agent include substitution of various amino acids for glycine residue in MAG3 and technetium-99m labeled organic cations.

Animals↗
PubMed2003

Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases.

Rhenium-188-HEDP ((188)Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of metastatic bone pain. As a product of (188)W/(188)Re generator, it is convenient for clinical therapeutic use with a short physical half-life of 16.9 h and a maximal beta-energy of 2.1 MeV. We investigated the effect of (188)Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 27 patients with bone metastases induced from prostate cancer. All patients were interviewed using a standardised set of questions before, and after therapy for 12 weeks. The patients were treated with 2700-3459 MBq of (188)Re-HEDP. Blood samples were taken weekly for 12 weeks, and a blood count was performed. Patients described an improvement on the Karnofsky performance scale from 74+/-7 to 85+/-9% 12 weeks after therapy (P=0.001). The pain score showed a maximum decrease from 44+/-18 to 27+/-20% in the third to the eight week after therapy (P=0.009). Seventy-six percent of the patients described a pain relief without increase of analgesic intake. Twenty percent of the patients could discontinue their analgesics and were pain free. Mean platelet count decreased from (286+/-75)*10(3) microl(-1) to (215+/-92)*10(3) microl(-1), and mean leucocyte count from (7.7+/-1.5)*10(3) microl(-1) to (6.0+/-1.9)*10(3) microl(-1) in the second to the fourth week after therapy. The maximal differences between the values of platelets and leucocytes before and after therapy were not statistically significant (P=0.021 and 0.094). In conclusion, (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain in prostate cancer and shows minimal bone marrow toxicity.

Aged↗
PubMed1998

Pharmacokinetics of 99Tcm-pertechnetate and 188Re-perrhenate after oral administration of perchlorate: option for subsequent care after the use of liquid 188Re in a balloon catheter.

Radioactive wires and other linear sources are currently being used in clinical trials as endovascular brachytherapy to prevent restenosis after percutaneous transluminal coronary angioplasty. A new concept is the use of a liquid-filled balloon containing a beta-emitting radioisotope. A major advantage is optimal delivery of the radioactivity to the vessel wall. Rhenium-188 (188Re) is a high-energy beta-emitter that is routinely available from a 188W/188Re generator in liquid form. Since 188Re-perrhenate could be released in the unlikely event of balloon rupture, we investigated whether, in analogy to pertechnetate, subsequent use of perchlorate can reduce the uptake of perrhenate in the thyroid. We performed static (n = 9) and dynamic (n = 11) thyroid scintigraphy with 99Tcm-pertechnetate to estimate the overall reduction in activity within 30 min and the washout from the thyroid after oral administration of 600 mg perchlorate (T1/2). In two patients, 188Re was injected to estimate the whole-body distribution and the discharge of thyroid activity after perchlorate use. Based on MIRD Dose Estimate Report No. 8 (valid for 99Tcm-pertechnetate), the radiation burden was calculated for intravenous administration of 188Re and competitive blocking with perchlorate. In 20 patients, 99Tcm uptake by the thyroid was reduced by 85% within 30 min by perchlorate. The mean (+/- S.D.) washout rate (T1/2) was 8 +/- 2 min in 11 patients. Perrhenate showed a whole-body distribution similar to that of pertechnetate and the thyroid activity could be displaced (T1/2 = 6.3 and 9.3 min, respectively) by oral administration of perchlorate, with reductions in uptake of 83% and 75% within 30 min, respectively. Whole-body scanning demonstrated no regional accumulation of 188Re-perrhenate with excretion by urine. Dose estimates gave an effective dose equivalent of 0.42 mSv MBq-1, which decreased to 0.16 mSv MBq-1 after perchlorate blocking. 188Re has favourable properties for endovascular brachytherapy via a balloon catheter and, in the unlikely event of balloon rupture, whole-body radiation can be reduced to 38% by subsequent oral administration of perchlorate.

Administration, Oral↗
PubMed2005

99mTc carbonyl t-butyl isonitrile: a potential new agent for myocardial perfusion imaging.

OBJECTIVE: The recent development of mixed ligand complexes using a 99mTc tricarbonyl synthon has prompted us to revisit the first generation product, 99mTc-t-butyl isonitrile (TBI), for possible myocardial imaging after modification of the 99mTc core to a mixed ligand core of carbonyl and t-butyl isonitrile. The easy availability of TBI from commercial sources and the recent promising development of a 'kit' procedure to prepare the 99mTc tricarbonyl aqua synthon/precursor [99mTc(H2O)3(CO)3]+ were other factors that triggered this work. METHODS: The carbonyl precursor (37-370 MBq/0.5 ml) was synthesized and reacted with TBI (3 mg.ml-1) at room temperature and at pH 8 for 1 h. [99mTc(CO)3(TBI)3]+ was characterized by C18 reverse phase HPLC in gradient mode with water and acetonitrile as solvent. Biodistribution studies were carried out in normal mice and planar images were acquired in rabbit at 5 min, 30 min, 1 h, 2 h and 4 h post-injection to assess heart uptake and soft tissue retention. [99mTc(CO)3(TBI)3]+was formed as a single species in >95% yield and was found to be stable. Biodistribution studies in mice revealed 2.3 (+/-0.2)% uptake in heart at 5 min p.i. with heart/liver, heart/lung and heart/blood ratios of 1.5, 2.0 and 30, respectively. Imaging studies in rabbits showed high uptake in myocardium, with negligible activity in blood and lungs, at 5 min p.i. that washed out of the heart after 4 h. CONCLUSION: [99mTc(CO)3(TBI)3]+ could be prepared in >95% yields. The complex showed high myocardial uptake with desirable rate of washout from heart in rabbits. [99mTc(CO)3(TBI)3]+ has potential to extend to larger animal studies and later for clinical evaluation as a myocardial imaging agent.

Animals↗
PubMed1995

Diagnosis of renal artery stenosis: feasibility of combining MR angiography, MR renography, and gadopentetate-based measurements of glomerular filtration rate.

OBJECTIVE: Our aim was to evaluate the feasibility of combining in a single test (1) structural evaluation of renal arteries with MR angiography, (2) functional evaluation of global glomerular filtration rates calculated on the basis of plasma disappearance of gadopentetate dimeglumine, and (3) renographic analysis of individual kidneys based on the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine. SUBJECTS AND METHODS: We used unenhanced MR angiography to measure patency of the renal arteries in 10 healthy volunteers and in 10 patients with renal artery stenosis. Calculations of global glomerular filtration rate were based on measurements of plasma disappearance of gadopentetate dimeglumine as shown by MR relaxometry. For renography with gadopentetate dimeglumine, we generated curves that showed changes in signal intensity in both kidneys over time; intrarenal kinetics were studied by measuring the time of arrival of gadopentetate dimeglumine in the cortex and outer medulla of the kidney. Conventional angiograms, measurements of global glomerular filtration rate based on plasma disappearance of 99mTc-DTPA, and 99mTc-DTPA renograms were used as reference standards. We compared the two different methods of determining global glomerular filtration rates by computing the correlation coefficient of the linear regression of rates derived from studies with gadopentetate dimeglumine versus rates derived from studies with 99mTc-DTPA. RESULTS: In all volunteers, renal arteries were well visualized, and global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine were normal. In nine of 10 patients, correlation was good between findings on MR angiograms and findings on conventional arteriograms. Finding were discordant in one patient because the patient moved during the MR angiography. For all six patients studied, correlation was good between measurements of global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine and those based on clearance of 99mTc-DTPA (r = 98%). CONCLUSION: Our results suggest the potential of magnetic resonance for a comprehensive approach for detection of renal artery stenosis. This novel approach provides structural evaluation of renal arteries with unenhanced MR angiography. MR renography is done and global glomerular filtration rates are determined by using MR relaxometry after injection of contrast material. Corticomedullary transit times can be determined on the basis of the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine.

Adult↗
PubMed1996

Aerosol deposition in infants with cystic fibrosis.

Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 microns mass median diameter (MMD); group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 microns. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 +/- 0.35% and 0.76 +/- 0.36%, respectively. In group C, 2.0 +/- 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 microns MMD) was deposited in the lung better than large particles.

Aerosols↗
PubMed2001

Transfer of the human NaI symporter gene enhances iodide uptake in hepatoma cells.

UNLABELLED: The characteristic feature of thyroid cells of taking up iodide enables benign thyroid diseases and differentiated thyroid carcinoma to be successfully treated with radioiodide therapy. The transport of iodide across the cell membrane is mediated by the human NaI symporter (hNIS). We therefore investigated whether the accumulation of iodide may be induced by the retroviral transfer of the hNIS gene in nonthyroid tumor cells. METHODS: With use of a bicistronic retroviral vector for the transfer of the hNIS coding sequence and the hygromycin resistance gene, rat Morris hepatoma (MH3924A) cells were infected with retroviral particles and 32 hNIS-expressing cell lines were generated by hygromycin selection. After incubation of the genetically modified and wild-type hepatoma cells and the rat thyroid cell line FRTL5 with Na125I, the uptake and efflux of iodide were determined. In addition, the iodide distribution in rats bearing wild-type and genetically modified hepatomas was monitored. RESULTS: Genetically modified MH3924A cell lines accumulated up to 235 times more iodide than did noninfected hepatoma cells. The maximal iodide uptake in the cells was observed after 60 min incubation time. Competition experiments in the presence of sodium perchlorate revealed a dose-dependent decrease of iodide uptake (87%-92%). Moreover, carbonyl cyanide p-trifluoromethoxyphenylhydrazone led to a loss of accumulated I- (32%), whereas 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene increased the I- uptake into the cells (22%). However, a rapid efflux of the radioactivity (80%) was observed during the first 10 min after 125I(-)-containing medium had been replaced by nonradioactive medium. In rats, the hNIS-expressing tumors accumulated six times more iodide than did the contralateral wild-type tumor as monitored by scintigraphy. The ex vivo quantitation of the iodide content performed 1 h after tracer administration in 1 g of tumor tissue revealed a 17-fold higher iodide accumulation in the genetically modified tumors. In accordance with the in vitro data, we also observed a rapid efflux of radioactivity from the tumor in vivo. CONCLUSION: The transduction of the hNIS gene per se is sufficient to induce 125I transport in Morris hepatoma cells in vitro and in vivo. With regard to a therapeutic application, however, additional conditions need to be defined that inhibit the iodide efflux from the tumor cells.

Animals↗
PubMed2000

Comparison of in vitro and in vivo efficiencies of a novel unit-dose liquid aerosol generator and a pressurized metered dose inhaler.

Gamma scintigraphic imaging was employed in 10 healthy volunteers to compare the total and regional lung deposition of aerosols generated by two delivery platforms that permitted microprocessor-controlled actuation at an optimal point during inhalation. An aqueous solution containing 99mTc-DTPA was used to assess the deposition of aerosols delivered by inhalation from two successive unit-dosage forms (44 microl volume) using a prototype of a novel liquid aerosol system (AERx Pulmonary Delivery System). This was compared with aerosol deposition after inhalation of two 50 microl puffs of a 99mTc-HMPAO-labeled solution formulation from a pressurized metered dose inhaler (MDI). The in vitro size characteristics of the radiolabeled aerosols were determined by cascade impaction. For the AERx system, the predicted lung delivery efficiency based on the product of emitted dose (60.8%, coefficient of variation (CV)=12%) and fine particle fraction (% by mass of aerosol particles <5.7 microm in diameter) was 53.3% (CV=13%). For the solution MDI, the emitted dose was 62.9% (CV=13%) and the predicted lung dose was 44. 9% (CV=15%). The AERx system demonstrated efficient and reproducible dosing characteristics in vivo. Of the dose loaded into the device, the mean percent reaching the lungs was 53.3% (CV=10%), with only 6. 9% located in the oropharynx/stomach. In contrast, the lung deposition from the solution MDI was significantly less (21.7%) and more variable (CV=31%), with 42.0% of the radiolabel detected in the oropharynx/stomach. Analysis of the regional deposition of the radioaerosol indicated a homogeneous pattern of deposition after delivery from the AERx system. A predominantly central pattern of distribution occurred after MDI delivery, where the pattern of deposition was biased towards a central zone depicting the conducting airways. The AERx system, in contrast to MDIs, seems highly suited to the delivery of systemically active agents via pulmonary administration.

Adult↗
PubMed2001

Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.

To establish an effective nonviral gene delivery and a corresponding imaging method for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were (111)In labeled through a diethylenetriaminepentaacetic acid chelate. (111)In-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. (111)In-oligo/G4-Bt and (111)In-oligo-Bt were conjugated to avidin ((111)In-oligo/G4-Av and (111)In-oligo-Av, respectively). (111)In-oligo/G4, (111)In-oligo/G4-Av, (111)In-oligo-Av, and carrier-free (111)In-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of (111)In-oligo-carrier complexes or (111)In-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after i.p. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of (111)In-oligo-carrier complex or (111)In-oligo (1.85 MBq/2.2 ng). (111)In-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of (111)In-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of (111)In-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver (111)In-oligo to i.p.-disseminated tumors. (111)In-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery.

Animals↗
PubMed1983

[Measurement of the right ventricular ejection fraction during the acute phase of myocardial infarction using 81m krypton infusion. Comparison with the left ejection fraction].

The right ventricular ejection fraction is rarely measured, as conventional diagnostic methods (radiology, echocardiography) are confronted with the problem of representing the right ventricle as a simple tridimensional geometrical model. This is not necessary with the radio-isotopic techniques. However, all those used for the measurement of right ventricular ejection fraction lead to important methodological problems. We have therefore developed a technique of measuring this parameter with an infusion of 81 m Kr. This radioactive gas is pure gamma-ray emitter with a 13 second period. Dissolved and infused intravenously, it is eliminated during the first passage through the lung. The continuous separation of the generator of 81 m Kr is performed with isotonic dextrose solution which is then infused for a period of 7 minutes. During this time, the activity detected by the scintillation camera inclined in the 30 degrees RAO projection is stored, together with the electrocardiogram in a computer. The precordial radioactivity of the retrocardiac lung tissue is subtracted after injection of 74 MBq of 99 mTc microspheres. A graph of right ventricular activity can then be reconstructed and the right ventricular ejection fraction calculated. The left ventricular ejection fraction is then measured with 99 mTc--labelled RBCs. This method allows the right ventricular ejection fraction to be measured in the RAO projection, the best incidence for the separation of the right atrial from the right ventricular activity without interference from left ventricular activity because of the pulmonary elimination of the Krypton radioactivity. The measurement performed on a large number of cardiac cycles allows a continuous study of the right ventricular ejection fraction. At the end of the infusion there is no circulating radioactivity so that the measurement can be repeated. This technique was used in 17 patients with acute myocardial infarction. In the 7 patients with anterior infarcts reduction of the left ventricular ejection fraction was the predominant finding (21,6 +/- 6,8%). The right ventricular ejection fraction was 34,2 +/- 6,4%. On the other hand, patients with a postero-inferior infarction had little change in left ventricular ejection fraction (59,2 +/- 12%) but those with right ventricular extension of their infarcts had very reduced right ventricular ejection fractions (less than 23%). The measurement of right ventricular ejection fraction with 81 m Kr is a reliable atraumatic method for diagnosing right ventricular infarction by the quantification of its functional impairment.

Adult↗