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What is the role of bone scintigraphy in the diagnosis of infected joint prostheses?

AIM: To analyse the role played by bone scintigraphy in the diagnosis of infected joint prostheses. METHODS: The study included 77 patients, aged 32-77 years, in whom infection of a joint prosthesis (48 hip, 29 knee) was suspected. In all patients the following examinations were performed consecutively: a two-phase Tc methylene diphosphonate (Tc-MDP) bone scan, a Tc hexamethylproplyene amine oxime (Tc-HMPAO) labelled white blood cell (WBC) scan, and a Tc microcolloid bone marrow (BM) scan. The minimum interval between examinations was 48 h. The diagnoses were based on data obtained from bacteriological cultures. RESULTS: The bone scan was positive in all patients and 28 of them had an infection (sensitivity 100%, specificity 0%). The WBC scan was positive in 61 patients but only 27 had an infection. The WBC scan was negative in 16 patients, and the possibility of infection was discarded in 15 of these cases (sensitivity 96%, specificity 30%). The results of the bone marrow scan were not compatible with those of the WBC scan (suggestive of infection) in 27 patients: 26 of them had prosthesis infection. The results of both examinations were compatible in the other 34 patients and the possibility of infection was discarded in 33 of these patients (sensitivity 92.8%, specificity 98%). The addition of a BM scan to a WBC scan decreased the sensitivity from 96% to 92.8% but increased specificity from 30% to 98%. The addition of a bone scan to this dual combination did not alter the results. CONCLUSIONS: When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed, if positive, by a BM scan. This procedure reduces the cost, the time required for a diagnosis, and the dose of radiation received by the patient.

Adult↗

Further studies on spot tests and microcrystal tests for identification of cocaine.

The presence of cocaine in illicit drug samples is still being determined in some laboratories using spot tests and microcrystal tests. Seventeen chemical species were tested using three different spot tests (Wagner, Marquis, and cobalt thiocyanate followed by stannous chloride reactions) and two microcrystal tests (gold chloride and platinic chloride) to determine whether the results could be differentiated from the results of these tests on cocaine. The data obtained indicated that nine of the 17 compounds gave results similar to those from cocaine using the three spot tests, but that the results from microcrystal testing allowed for differentiation of all nine compounds from cocaine.

Cobalt↗

Pattern of organotin inhibition of methanogenic bacteria.

Seven organotin compounds and tin chloride were tested for their effects on the methanogenic bacteria Methanococcus thermolithotrophicus, Methanococcus deltae delta LH, and Methanosarcina barkeri 227. The methanogens were strongly inhibited by triethyltin, tripropyltin, and monophenyltin compounds, generally at concentrations below 0.05 mM. Less inhibition by tributyltin and diphenyltin was observed at levels below 0.1 mM, but complete inhibition was observed at a 1 mM concentration. Tin chloride inhibited all methanogens, with nearly complete inhibition at a 1 mM concentration. There was no inhibition by tetra-n-butyltin and triphenyltin compounds even at 2 mM, the highest concentration tested. The 50 and 100% inhibitory concentrations of all compounds were estimated; these values varied with both the compound tested and the bacterium tested. The 50% inhibitory concentration estimate generally decreased (i.e., giving a higher toxicity) as the total surface area of the alkyltin molecules decreased. These results differ considerably from those reported previously for aerobic microorganisms (G. Eng, E. J. Tierney, J. M. Bellama, and F. E. Brinckman, Appl. Organometallic Chem. 2:171-175, 1988), where a clear correlation between increasing total molecular surface area and increasing toxicity was documented with a variety of organisms. Using the same procedures as for the methanogens, we examined the effects of organotin compounds on Escherichia coli growing aerobically or anaerobically. The E. coli inhibition pattern clearly resembled that seen in the data of Eng et al., under both aerobic and anaerobic conditions.

Escherichia coli↗

Technetium-99m labeling of a molecule bearing easily reducible groups.

Chemical stability of the naphthol-azo dye Evans Blue (EB) was examined in the presence of acidic stannous chloride (SnCl(2)), with a view to preparing an instant cold kit. EB was found to be reactive toward this reducing agent, yielding the metal-chelating molecule 1,7-diamino-8-naphthol-2,4-disulfonic acid at high acidity and high stannous concentrations. This reduction reaction was undesirable in the cold kit preparation. The conditions were determined where reduction was inhibited, at pH = 5.0 and with a mole ratio of EB to SnCl(2) = [10:1], effecting the facile preparation of stable cold kits. Successful (99m)Tc-labeling of an EB cold kit using these conditions resulted in the desired product with 98% radiochemical purity. Based on the radiolabeling efficiencies of chosen model compounds, it was rationalized that (99m)Tc metal predominantly coordinated with the 1-amino-8-hydroxy groups in the EB molecule to form (99m)Tc-EB.

Chelating Agents↗

A study of colloidal scintigraphy in alcoholic liver diseases: discordance from asialo-scintigraphic findings.

BACKGROUND: Our study was undertaken to check the discordance between findings from 99mTc-Sn colloidal reticuloendothelial scintigraphy (RESS) and 99mTc-GSA asialo-scintigraphy (GSA, a technique for evaluation of liver parenchymal cell density and function) and to analyze the discordance in relation to functional disturbances. We compared data between patients with alcoholic liver diseases (ALD) and patients with viral liver diseases (VLD). METHODS: The subjects of this study were 40 patients with chronic liver disease (17 with ALD and 23 with VLD). We used the liver uptake ratio of the tracer of the Sn colloid (SnL15, %), the liver uptake rate (GSAL15, %), and the Rmax (an indicator of total liver receptors) as indices of liver scans. RESULTS: GSAL15 was sometimes nondiscordant from SnL15. The patients were divided into two groups: the nondiscordant group (26 cases where the balance/sum of the two variables was <25%) and the discordant group (14 cases where the balance/sum was > or =25%). SnL15 was 41.6 +/- 16.2% in the nondiscordant group and 42.7 +/- 16.3% in the discordant group (p = 0.80). GSAL15 was 34.3 +/- 12.1% in the nondiscordant group and 21.5 +/- 8.1% in the discordant group (p = 0.001). Rmax was 0.33 +/- 0.17 in the nondiscordant group and 0.113 +/- 0.008 in the discordant group (p = 0.002). Thus, the SnL15, as determined by RESS, did not differ significantly between the nondiscordant and discordant groups, whereas GSAL15 was significantly unfavorable in the discordant group as compared with the nondiscordant group. SnL15 as determined by RESS did not differ significantly between the ALD group (40.4 +/- 18.7%) and the VLD group (43.5 +/- 15.0%) (p = 0.59), whereas Rmax as determined by GSA was significantly improved in the ALD group (0.34 +/- 0.20) compared with the VLD group (0.20 +/- 0.4) (p = 0.02). CONCLUSIONS: Liver cell function was lower in cases that showed discordance between liver cell function and reticuloendothelial function compared with cases without such discordance, although reticuloendothelial function did not differ between discordant and nondiscordant groups. Liver cell function was better in cases of ALD than in cases of VLD, whereas reticuloendothelial function did not differ between the ALD group and the VLD group.

Adult↗

[The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid].

Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve.

Adult↗

[Evaluation of liver function in carbon tetrachloride-damaged rabbits by dynamic SPECT: comparison of 99mTc-GSA and 99mTc-Sn colloid].

Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new ligand that binds specifically to asialoglycoprotein receptors in hepatocytes. We performed liver dynamic SPECT using 99mTc-GSA and 99mTc-Sn colloid in nine normal control rabbits and 17 chronically CCI4-damaged rabbits (total 29 examinations), and also performed liver function tests (ICGR15, Alb, etc). Using the obtained dynamic SPECT data, we analyzed the liver kinetics of 99mTc-Sn colloid using a one-compartment model (hepatic blood flow [K]) and 99mTc-GSA using a two-compartment model (hepatic blood flow and receptor binding [K1], catabolism [K2]). As the CCl4-treated period increased, K1 decreased most significantly. K1 showed the most significant statistical correlation with the results of liver function tests, ICGR15 (p < 0.0001), Alb, PT, HP, Bil and GPT. Further, only K1 showed a correlation with the hepatic fibrosis of the HAI score. From the present results, liver dynamic SPECT using 99mTc-GSA may be said to provide a novel method for the evaluation of hepatic functional reserve.

Animals↗

A new 99mTc labelling method for leucocytes: in vitro and in vivo comparison with 99mTc-HMPAO.

A new method for the labelling of mixed leucocytes with 99mTc-tropolone was optimized and compared with a 99mTc-HMPAO leucocyte labelling procedure in vitro and in vivo. In the present study, leucocytes obtained from patients suffering from Crohn's disease, were isolated and labelled with 99mTc-HMPAO or labelled according the new 99mTc-tropolone procedure using 9.8 mM tropolone, 1 microM stannous chloride and 0.8 mM potassium borohydride (KBH4) at pH 5.5-6. Labelling efficiency with 99mTc-tropolone yielded 92 +/- 3%, which is higher compared to the 99mTc-HMPAO labelling procedure (64 +/- 13%) using 10(8) of leucocytes. In vitro stability and viability of both the tropolone and the HMPAO labelled cells was investigated. The viability test of the 99mTc-labelled leucocytes was performed in autologous plasma at 37 degrees C and compared with unlabelled leucocytes. After 18 hours of incubation a significant (P < 0.05) higher stability was observed for 99mTc-tropolone labelled leucocytes (84 +/- 5%) compared with that of 99mTc-HMPAO labelled leucocytes (73 +/- 5%). The viability of the 99mTc-labelled leucocytes observed for both labelling procedures was similar to unlabelled leucocytes. In vivo experiments were performed in mice. 99mTc-tropolone or 99mTc-HMPAO labelled murine mixed leucocytes were injected in mice, with a Staphylococcus aureus ATCC 25923 thigh infection. Analysis of scintigraphic images yielded a faster clearance of the 99mTc-tropolone labelled leucocytes. This was most likely due to a significant (P < 0.02) higher liver uptake at 4 hours after administration of the 99mTc-tropolone labelled leucocytes (19%) in comparison with 99mTc-HMPAO labelled cells (9%). Faster and significant (P < 0.02) higher accumulation of the 99mTc-tropolone labelled leucocytes was observed at the site of infection compared with 99mTc-HMPAO labelled leucocytes at all time-intervals after the administration of the 99mTc-labelled leucocytes. The new 99mTc-tropolone leucocyte labelling procedure, offers an attractive low-cost agent for research purposes.

Abscess↗

Labelling, control and radiopharmacological evaluation of 99mTc-adenosine 5'-diphosphate (99mTc-ADP) as tumour seeking agent.

A study of 99mTc-adenosine-5'-diphosphate (99mTc-ADP) as a radiopharmaceutical for tumour diagnosis is presented. Two different labelling methods, using SnCl2 in alkaline solution and Zn as reducing agents, were developed. Reduction with Sn(II) alkaline solution was the selected method because a lower concentration of ADP (0.5 mg/mL) could be used and a higher radiochemical yield was achieved. A labelled molecule with a radiochemical purity higher than 95%, in vitro stability of at least 6 hours and an over all negative charge was obtained Biodistribution studies carried out in normal mice and rats revealed rapid urinary excretion and no specific accumulation of activity in any other particular organ. This behaviour was similar to that reported for 99mTc-adenosine-5'-triphosphate (99mTc-ATP). Rapid blood clearance, that could be fitted to a bicompartimental model, was also verified. No evidence of in vivo instability was observed. Studies in mice and rats bearing spontaneous mammary adenocarcinomas were performed and the results were compared to those from the 99mTc-ATP studies. Although the tumour models used were not the same, the incorporation of both labelled compounds was very similar. Radioactivity uptake in the tumour and the tumour-to-blood ratio were not notably high. However, a significant increment was observed in the tumour-to-muscle ratio (1.0 +/- 0.2 at 30 minutes to 2.7 +/- 0.4 at 240 minutes). Whole-body autoradiography enabled tumour visualization. Further investigations, including scintigraphic imaging, must be carried to complete the clinical evaluation of 99mTc-ADP as a tumour seeking agent.

Adenocarcinoma↗

Towards developing a non-SnCl2 formulation for RP444, a new radiopharmaceutical for thrombus imaging.

There are many factors influencing the yield and radiochemical purity (RCP) of the radiopharmaceutical RP444. These include heating temperature, heating time, pH, the use of a buffering agent and a bulking agent, as well as the component (XV066, tricine, TPPTS, and Na99mTcO4) concentration. Through a series of radiolabeling experiments, we found that a formulation comprised of 20 microg of XV066, 6.5 mg of tricine, 40 mg of mannitol, 5 mg of TPPTS, and 0.1 mg of Pluronic acid dissolved in 1.0 mL of 250 mM succinate buffer (pH 5.0) gives the best RCP for RP444. The formulation can be lyophilized to form a stable crystal "cake". The radiolabeling is achieved by adding 1.5 mL generator eluant (33-133 mCi of Na99mTcO4) to a lyophilized vial and heating the reaction mixture at 100 degrees C for 10 min. Using this formulation, RP444 is prepared consistently in high yield with RCP > or = 90%. Formation of [99mTc]colloid is minimal (< 0.5%).

Chromatography, High Pressure Liquid↗

Dual isotope carotid scintigraphy in patients with amaurosis fugax attacks.

A new dual isotope scintigraphic (DISC) examination of the carotid arteries consisting of simultaneous injections of 111In-labeled platelets and 99mTc-labeled red cells was performed on eight male patients suffering from amaurosis fugax attacks. In concordance with the angiographically proven high percentage of significant extracranial carotid disease in patients with amaurosis fugax, six of the eight patients examined had an increased platelet accumulation in the carotid artery clinically affected. In one patient with normal angiography and one amaurosis fugax attack the platelet scintigraphy even revealed a pathological platelet accumulation in the ipsilateral carotid artery. These findings confirm the hypothesis that most amaurosis fugax attacks are due to arterio-arterial emboli originating from atherosclerotic plaques of the carotid bifurcation.

Aged↗

Particle sizing and biokinetics of interstitial lymphoscintigraphic agents.

The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.

Absorption↗

Reaction of optically active alpha-aminoallenylstannanes with aldehydes formed in situ from the Lewis-acid-catalyzed rearrangement of epoxides.

Reaction of optically active alpha-oxazolidinonylallenylstannanes with oxiranes in the presence of BF3.OEt2 produced beta-hydroxypropargylamines with high syn diastereoselectivity and high enantioselectivity through an initial Lewis-acid-catalyzed rearrangement of the oxirane to the corresponding aldehyde via an alkyl, aryl, or hydride shift. This permits the use of readily available oxiranes as alternatives to aldehydes that are difficult to prepare and/or unstable.

Acids↗