Assessment of various parameters in the estimation of differential renal function using technetium-99m mercaptoacetyltriglycine

Differential renal function (DRF) is an important parameter that should be assessed from virtually every dynamic renogram. With the introduction of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), a tracer with a high renal extraction, the estimation of DRF might hopefully become accurate and reproducible both between observers in the same institution and also between institutions. The aim of this study was to assess the effect of different parameters on the estimation of DRF. To this end we investigated two groups of children: group A, comprising 35 children with a single kidney (27 of whom had poor renal function), and group B, comprising 20 children with two kidneys and normal global function who also had an associated 99mTc-dimercaptosuccinic acid scan (99mTc-DMSA). The variables assessed for their effect on the estimation of DRF were: different operators, the choice of renal regions of interest (ROIs), the applied background subtraction, and six different techniques for analysis of the renogram. The six techniques were based on: linear regression of the slopes in the Rutland-Patlak plot, matrix deconvolution, differential method, integral method, linear regression of the slope of the renograms, and the area under the curve of the renogram. The estimation of DRF was less dependent upon both observer and method in patients with two normally functioning kidneys than in patients with a single kidney. The inter-observer comparison among children in either group was not dependent on either ROI or background subtraction. However, in patients with poor renal function the method of choice for the estimation of DRF was dependent on background subtraction, though not ROI. In children with two kidneys and normal renal function, the estimation of DRF from the 24 techniques gave similar results. Methods that produced DRF values closest to expected results, from either group of children, were the Rutland-Patlak plot and matrix deconvolution methods.     

Effect of histamine on technetium-99m excretion by gastric mucosa

The ability of histamine to increase excretion of 99mtechnetium by gastric mucosa was investigated in dogs with Heidenhain pouches and denervated antral pouches. Histamine increased Heidenhain pouch 99mtechnetium output in a dose-related manner, and 99mtechnetium output was related linearly to acid output. Antral pouch 99mtechnetium output was unchanged by increasing doses of histamine. The study suggests that concomitant use of histamine may improve the accuracy of 99mtechnetium scanning in the clinical diagnosis of conditions caused by ectopic gastric mucosa.     

Biliary excretion of Tc-99m EC in renal studies

The role of biliary excretion in Tc-99m ethylenedicysteine (EC) renal imaging was studied. Of 2,215 dynamic renal studies performed with Tc-99m EC, only nine cases of gallbladder visualizations and/or biliary excretion were identified. In no case did biliary excretion affect the interpretation of the renal study.     

Dynamic scintiscanning with technetium-99m as a diagnostic aid in oliguria after renal transplant

Scanning with technetium-99m was used as a diagnostic aid in renal transplant patients with post-transplant oliguria. It is a safe and dependable method of determining whether the renal vasculature is still intact and can often be used to differentiate acute tubular necrosis from acute rejection.     

Anomalies in hepatobiliary excretion of technetium-99m-MAG3 preparations

Technetium-99m-MAG3 is accepted as a renal tubular function agent. However, sporadic liver and gall bladder visualisation during its clinical use is clearly a disadvantage. HPLC-purified 99mTc-MAG3 samples exhibited appreciable hepatobiliary uptake (7%), and an elevated level of such uptake was observed in unpurified kit preparations, which was stated to be associated with the excretory property of the radiolabeled kit impurities. To verify this we attempted to quantitate the hepatobiliary uptake of the kit preparations with that of its radiolabeled components. The contribution of each component toward hepatobiliary uptake of the sample was calculated from their abundance in the chelate mixture and the individual biodistribution of the isolated components. However, the anticipated hepatobiliary uptake of different preparations of 99mTc-MAG3 calculated in this way was always lower than that of the experimental value determined directly. Further work is needed to explain the anomaly.     

Prospective identification of myocardial stunning using technetium-99m sestamibi-based measurements of infarct size

OBJECTIVES: We sought to prospectively identify patients with stunning and hyperkinesia at hospital discharge on the basis of mismatches between left ventricular (LV) function and infarct size as assessed by technetium-99m (Tc-99m) sestamibi perfusion tomographic imaging. BACKGROUND: Mechanical indexes of LV function may not accurately reflect myocardial damage after acute myocardial infarction (MI) because of myocardial stunning and compensatory hyperkinesia in noninfarct-related territories. Myocardial perfusion techniques are unaffected by these variables. METHODS: Eighty-four patients with acute MI underwent hospital admission and discharge Tc-99m-sestamibi tomographic imaging. Global LV ejection fraction (LVEF) was measured at hospital discharge and 6 weeks later. The perfusion defect size was quantified and expressed as a percentage of the LV. The discharge perfusion defect, which is a measure of infarct size, was used to predict the 6-week LVEF for each patient based on a previously reported regression equation. Patients were classified into one of three groups depending on whether their LVEF at hospital discharge fell within, above or below one standard error (6.8 LVEF points) of the predicted 6-week LVEF. RESULTS: There were 48 patients classified as having a "match" between function and infarct size; these patients demonstrated no significant change in LVEF at 6 weeks. There were 21 patients (25%) classified as "mismatch stunned" who had discharge LVEFs lower than those predicted by infarct size. These patients demonstrated a significant improvement in mean LVEF at 6 weeks (mean [+/-SD] discharge LVEF 0.41 +/- 0.08, 6-week LVEF 0.47 +/- 0.10; p = 0.003). Fifteen patients (18%) were classified as "mismatch-hyperkinetic." The mean LVEF for these patients significantly declined at 6 weeks (discharge LVEF 0.64 +/- 0.06, 6-week LVEF 0.58 +/- 0.09; p = 0.002). There was a marked increase in LVEF within the infarct zone (8 +/- 15 LVEF points; p = 0.03) for patients predicted to have stunning and a marked decline in LVEF outside the infarct zone (9 +/- 15 LVEF points; p = 0.06) in patients predicted to have hyperkinesia. Both discharge LVEF (p < 0.0001) and group classification (p = 0.005) were independent predictors of LVEF 6 weeks later. CONCLUSIONS: Perfusion imaging with Tc-99m-sestamibi can identify post-MI patients at hospital discharge in whom LV function is discordant with the measured infarct size. Patients with stunning have late increases in LVEF; patients with hyperkinesia have late decreases. This methodology, performed at discharge, is predictive of late changes in LV function.     

Hypertension in paediatrics: can pre- and post-captopril technetium-99m dimercaptosuccinic acid renal scans exclude renovascular disease?

The presence of biogene monoamines in adult and larval Diphyllobothrium dendriticum (Cestoda) was investigated by high-performance liquid chromatography with electrochemical detection (HPLC-ED). The biogene amines serotonin (5-HT), dopamine (DA), noradrenaline (NA), and adrenaline (A) as well as many of their precursors and metabolites, comprising a total of 15 different substances, were analyzed. 5-HT, DOPA, DA, NA, and A were detected in the worm, with 5-HT, DOPA, and DA being the dominating amines. The DA metabolites DOPAC and 3-MT or the 5-HT precursor 5-hydroxytryptophan could not be detected, but two unidentified substances, believed to be catecholic, were present in the worm. A high concentration of DOPA was measured in the proglottids and especially in the eggs. This is the first report of A in a flatworm.     

Evaluation of the hepatobiliary excretion of technetium-99m-MAG3 and reconstitution factors affecting radiochemical purity

Technetium-99-MAG3 is a renal tubular function agent. However, sporadic liver and gallbladder visualization have raised questions about kit stability, impurities and nonrenal routes of excretion. To address these issues, studies were conducted to optimize the labeling efficiency of the TechneScan MAG3 kit and to evaluate the hepatobiliary excretion of the MAG3 complex. METHODS: Thirty-six vials of the commercial formulation of 99mTc-MAG3 were prepared according to manufacturer's instructions and evaluated for radiochemical purity using two methods: a combination of high-performance liquid chromatography and paper chromatography (HPLC/PC); and the manufacturer's miniature chromatography system (Sep-Pak procedure). RESULTS: The labeling efficiency was significantly higher when the kit was reconstituted with 10 ml (96.6%) of saline versus 5 ml (91.4%) (p < 0.01). The radiochemical purity of the kits remained stable for up to 6 hr, but the purity determined by Sep-Pak averaged 2.5% higher than that determined by HPLC procedures (p < 0.01). Rat studies to evaluate renal and hepatobiliary elimination of MAG3 showed no difference in the %ID excreted into the urine by 60 min in all groups of animals studied. However, the %ID excreted into the bile was significantly higher for the kit formulation than the HPLC-purified MAG3, 9.9% versus 6.6% (p = 0.0475). CONCLUSION: The radiochemical purity of the TechneScan MAG3 kit can be improved by reconstituting with larger volumes. In addition, the studies in rats suggest that fasting or kit impurities may be a contributing factor to increased hepatobiliary visualization in patient studies.     

Clinical evaluation of technetium-99m-L,L-ethylenedicysteine in patients with chronic renal failure

1. Effects of feeding condition from birth were examined on the sensitivity of neuromuscular transmission to d-tubocurarine (dTc) in vitro in male mice of the ddY strain. 2. Mice were trained to climb two separated cylindrical steel-wire tubes for feeding and drinking, respectively, from 16 days of age. Some mice were conventionally fed, from 99 days of age. Nerve-muscle preparations were made from the left phrenic nerve diaphragm muscle (DPH), the sciatic nerve soleus muscle (SOL), and the sciatic nerve extensor digitorum longus muscle (EDL) of 99-day-old and 155-day-old mice. The nerve trunk was electrically activated with trains of four pulses and tetanic pulses. 3. The sensitivity to the effects of dTc decreased in the order EDL, SOL, and DPH. This result held true in all mice tested. 4. This sensitivity was significantly potentiated by the compulsory movement. 5. The supersensitivity remained even when mice were conventionally fed after 99 days of age. 6. The compulsion rendered EDL antifatigable on tetanic stimulation. This property was also retained after a return to conventional feeding. 7. These results suggest that the effects of feeding condition from birth might remain on neuromuscular functions after termination of the conditioning.     

Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide

Genetic structure of bank vole populations in linear river bank habitat in southeast Norway was determined from analyses of DNA sequences for the mitochondrial D-loop. Animals were sampled at sites separated by 1 km, along two forested river banks separated by approximately 100 m of open water. Twenty-six distinct haplotypes were found among 120 voles. The voles showed significant deviation from panmixis on both sides of the river. Animals from the same site or from sites 1 km apart were more likely to share haplotypes than animals 2 km apart or more. Common haplotypes were widespread on both river banks, and had a wider distribution than relatively rare haplotypes. Some rare haplotypes were found on both banks, but most were restricted to a single bank. The results suggest that short-term gene flow may be restricted for female bank voles in linear habitats. Female territorial behaviour may vary with habitat geometry. In the linear habitat described here, females defend only two territorial borders and may effectively limit female dispersal. Results were compared to a previous study of bank voles from this region in a two-dimensional habitat. Gene flow in the linear habitat was much more restricted than gene flow in the two-dimensional habitat. Probable mechanisms underlying this difference are discussed.     

Role of technetium-99m sestamibi in localisation of thyroid cancer metastases

Technetium-99m sestamibi (MIBI) is a routinely used myocardial perfusion imaging agent. We have studied groups of patients with differentiated thyroid carcinoma, in order to evaluate the usefulness of this agent in localising regional neck and nodal disease and metastases. There are three groups of patients. Group 1 consisted of patients with known nodal disease or metastases (22 patients) and with raised serum thyroglobulin levels (Tg). Group 2 comprised patients with normal I-131 scans and normal Tg levels (nine patients). Non-thyroid malignancies (six patients) comprised an additional group 3. In group 1, the MIBI scan showed 47 sites of metastases, while the I-131 scan revealed 49 sites. The MIBI scan was positive in two patients where the I-131 scan was negative, while in two other patients, the MIBI study was negative whereas the I-131 scan was positive. In group 2, 6/9 patients had no disease, 2/9 had thyroid remnants, and 1/9 had a fresh primary lung tumour, unrelated to the earlier thyroid cancer. All of them had normal MIBI scans. In group 3, two patients with lung cancer and two with breast cancer and metastases had normal MIBI scans. A further two patients with nasopharyngeal cancer (NPC) had mildly increased MIBI localisation in neck nodes and bone metastases. In summary, Tc-99m sestamibi appears to be as good as I-131 in search for thyroid carcinoma metastatic spread, especially nodal disease and this tracer does not localise well in the primary or metastases of other cancers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dipyridamole technetium-99m Sestamibi imaging in the diagnosis of syndrome X

In a middle-aged woman with anginal chest pain and a normal-appearing angiogram, dypiridamole technetium-99m Sestamibi scintigraphy, a noninvasive method, provided the diagnosis of syndrome X and was used in follow-up to monitor the course of disease.     

Imaging of dopamine transporters in humans with technetium-99m TRODAT-1

Technetium-99m TRODAT-1, a tropane derivative, has shown promise as a tracer for the imaging of dopamine transporters in preliminary studies in rats and baboons. The present report concerns the first study of the use of [99mTc]TRODAT-1 for the same purpose in humans. The specific uptake of [99mTc]TRODAT-1 in dopamine transporter sites located in the basal ganglia area was confirmed: the best contrast between the basal ganglia and the occipital area, which is devoid of dopamine transporters, was achieved at 120-140 min following injection. The development of a 99mTc-based agent bypasses the need for cyclotron-produced radionuclides, which will be of benefit for routine clinical studies.     

Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters

Technetium-99m TRODAT-1 is an analog of cocaine that selectively binds the presynaptic dopamine transporters. The primary purpose of this study was to measure its whole-body biokinetics and radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. METHODS: The sample included 4 men and 6 women ranging in age from 22-54 yr. An average of 20 whole-body scans were acquired sequentially on a dual-head camera for up to 46 hr after the intravenous administration of 370+/-16 MBq (10.0+/-0.42 mCi) 99mTc TRODAT. The renal excretion fractions were measured from 12-24 discrete urine specimens. The fraction of the administered dose in 17 regions of interest and each urine specimen was quantified from the attenuation and background corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the Medical Internal Radiation Dose technique for each subject individually before any results were averaged. RESULTS: There were no pharmacological effects of the radiotracer on any of the subjects. The early planar images showed differentially increased activity in the nose, pudendum and stomach. SPECT images demonstrated that the radiopharmaceutical localized in the basal ganglia in a distribution that was consistent with selective transporter binding. Image analysis showed that the kidneys excreted between 20% and 32% of the injected dose during the first 22-28 hr postadministration, after which no more activity could be recovered in the urine. The dose limiting organ in both men and women was the liver, which received an average of 0.046 mGy/MBq (0.17 rads/mCi, range 0.14-0.22 rad/mCi). In the worst case, which was clearly an over-estimation, it would have taken 22.7 mCi to deliver 5 rad to the liver. CONCLUSION: TRODAT may be a safe and effective radiotracer for imaging dopamine transporters in the brain and the body.     

Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents

The synthesis and biodistribution in various animal models (rat, dog, pig and monkey) of 99mTc radiopharmaceuticals containing the Tc = N multiple bond are reported. METHODS: The complexes are represented by the general formula 99mTcN(L)2, where L is the monoanionic form of a dithiocarbamate ligand of the type [R1(R2)-N-C(=S)S]-, and R1 and R2 are variable, lateral groups. The preparations were carried out, both as a liquid and freeze-dried formulation, through a simple procedure involving the initial reaction of [99mTcO4]- with S-methyl N-methyl dithiocarbazate [H2NN(CH3)C(=S)SCH3], in the presence of tertiary phosphines or Sn2+ ion as reductants, followed by the addition of the sodium salt of the ligand (NaL) to afford the final product. The chemical identity of the resulting complexes was determined by comparing their chromatographic properties with those of the corresponding 99Tc analogs characterized by spectroscopic and x-ray crystallographic methods. The complexes are neutral and possess a distorted, square pyramidal geometry. RESULTS: No decomposition of the complexes, in physiological solution, was observed over a period of 6 hr. Imaging and biodistribution studies demonstrated that these radiopharmaceuticals localize selectively in the myocardium of rats, dogs and primates, but that they failed to visualize the pig heart. The kinetics of heart uptake and clearance were studied in rats and dogs, and found to be strongly influenced by variation of the lateral R1 and R2 groups. CONCLUSION: The high quality of myocardial images obtained in dogs and monkeys demonstrates that the derivative 99mTcN[E-t(EtO)NCS2]2 [99mTcN(NOEt)] exhibits the most favorable distribution properties for further studies in humans.     

Pentavalent technetium-99m dimercaptosuccinic acid uptake in primary amyloidosis: comparison with autopsy findings

Pentavalent technetium-99m labeled dimercaptosuccinic acid (99mTc(V)-DMSA) scanning was performed on a 71-year-old woman with histologically confirmed primary amyloidosis. Definite uptake of the tracer was noted in the thyroid, liver, spleen, and kidney as well as in the heart. Three months later, she died of heart failure, and autopsy findings demonstrated diffuse deposits of AL-type amyloid in those organs that were consistent with the accumulation of 99mTc(V)-DMSA.     

Intra-aortic injection of myoblasts in mdx mice: genetic and technetium-99m cell labeling and biodistribution

With the advance of chronobiology, demands for simultaneous long-term monitoring and recording of various biosignals are increasing. To meet these demands we have developed a portable multipurpose recording system using a 24-hour ambulatory recorder. This technical achievement of less restrictive round-the-clock simultaneous recording of biosignals from not only the circulatory system, but also from the neurological and digestive systems of a subject in his/her daily life will contribute to clinical research on circadian variations of biosignals and EEG analysis during sleep.