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PubMed1999

Medicinal applications of heavy-metal compounds.

A brief summary of the key role for certain heavy-metal compounds in medicine is discussed, with a special focus on very recent findings in the following four topics: platinum anti-tumor compounds (novel mononuclear compounds, dinuclear compounds and trinuclear compounds with promising activity); ruthenium anti-tumor compounds (the first clinical trial for a Ru compound has begun); gadolinium NMR-imaging compounds (association with biomacromolecules is now possible); technetium compounds (the use of organometallic precursors opens a plethora of new species and enables the labeling of, for example, neurotransmitter molecules).

Antineoplastic Agents↗
PubMed2003

Interobserver variability of cerebral blood flow measurements obtained using spectral analysis and technetium-99m labeled compounds.

Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or technetium-99m ethyl cysteinate dimer (99mTc-ECD) enables the non-invasive estimation of absolute cerebral blood flow (CBF) to be determined by using spectral analysis (SA). We previously demonstrated the clinical use of SA; however, this method involves a few manual steps. The aim of this study was to evaluate the interobserver variability of CBF estimations made using SA and compare these results with those obtained by using graphical analysis (GA). In twenty patients with various brain diseases (27-74 years old), radionuclide angiography examinations were performed using 99mTc-labeled compounds (10 patients, 99mTc-HMPAO; 10 patients, 99mTc-ECD). Bilateral cerebral hemispheres were studied in all patients, and the brain perfusion index (BPI) values were estimated using SA and GA. The interobserver variability between two observers was then assessed. A good correlation between the BPI values assessed using both SA (BPI(S)) and GA (BPI(G)) was obtained. The correlation coefficient for BPI(S) (r = 0.987) was almost the same as that for BPI(G) (r = 0.982). The degree of interobserver variability was not affected by the measurement of elevated BPI values. Measurements carried out by two observers using both SA and GA exhibited a similar degree of interobserver variability. SA appears to have a satisfactory interobserver variability and may be more suitable for clinical applications.

Algorithms↗
PubMed1979

Complexing of reduced technetium and tin (II) by chelating phosphate compounds. I. Chemical state of technetium.

Complexing of reduced 99mTc, 99Tc and of 113Sn(II) by pyrophosphate was studied, using the in vivo distribution in the rat as an indicator for complex formation. 99mTc-pyrophosphate was only formed at very low technetium concentrations, otherwise colloid formation occurred. Reduced 99mTc in trace amounts and 113Sn(II) complexed equimolarly with pyrophosphate were concentrated in bone and excreted in urine in comparable amounts. The in vivo distribution of 32P-orthophosphate and -pyrophosphate was characterized by a considerable uptake in the liver and a poor urinary excretion. The distribution patterns of 32P-pyrophosphate, complexed equimolarly with tin(II), remained unchanged. Despite these findings it is concluded that real chelates are formed, since non-complexed reduced 99mTc was not concentrated in bone. Two variants of reduced technetium could be discerned: a 99mTc-kidney agent and a 99mTc protein-bound agent. Some evidence was found that reduced technetium may change its oxidation state, but it seems much more likely that both agents are technetium(IV) compounds. It is suggested that the kidney agent is hydrated technetium dioxide whereas the protein-bound agent is a charged technetium(IV) compound. Only hydrated technetium dioxide is obviously complexed by chelating phosphate compounds.

Animals↗
PubMed2005

Characterisation via electrospray ionisation multistage mass spectrometry of three related series of nitrido technetium complexes containing phosphinothiolate and dithiocarbamate ligands.

Nine nitrido technetium compounds comprising bis-substituted Tc(N)(PS)(2) (1-4) (PS = bidentate phosphinothiolate ligands) and Tc(N)(dtc)(2) (5, 6) derivatives (dtc = bidentate dithiocarbamate), and mixed-ligand Tc(N)(PS)(dtc) (7-9) species, were subjected to electrospray ionisation mass spectrometry and MS(n) experiments. Bis-substituted phosphinothiolato complexes 1-4 lead to the straightforward formation of dinuclear species reasonably originating from proton bound dimers. These dinuclear species do not show, under collisionally induced fragmentation processes, the formation of monomeric units but cleavages related to the ligand framework, thereby proving the high stability of the [Tc--H(+)--Tc] bond. Bis-dithiocarbamate compounds 5 and 6 show, instead, abundant [M+H](+), [M+Na](+) and [2M+Na](+) ions, and their collisionally induced fragmentations are highly favoured with cleavages related to the C--N and C--S bonds. During these processes, the coordination of a water molecule to [MH-L](+) product ions is observed, as proved by the collisionally induced H(2)O loss detected for this species. Mixed-ligand compounds 7 and 8 show the protonated molecules and Na(+)-cationised ions with fragmentation processes related to the dithiocarbamate moiety. This behaviour indicates that coordination of ether- and ester-substituted dithiocarbamates to the [Tc [triple chemical bond] N] group is weaker than that of phosphinothiolates. Conversely, diethyldithiocarbamate inserted in mixed complex 9 enhances both C--N and Tc--S bonds, and fragmentation processes suggest that metal-phosphinothiolate and metal-dithiocarbamate show comparable strength.

Hydrolysis↗
PubMed1980

[The radiation dose to the foetus during isotope investigations of the mother].

The radiation dose to the foetus from the application of five different 99mTechnetium compounds during isotope investigation of the mother was investigated. After i-v injection of 100 muCi (3.7 MBq) of 99mTc-compounds into pregnant rats, these were sacrificed during the first, second and third week of pregnancy and radioactivity was determined in the foetuses and in the blood and organs of the mother. From these measurements the proportion of total body activity in individual organs and their specific activity was calculated. From this data the radiation burden to the rat foetuses from the various 99mTc compounds could be evaluated. Making use of phantom studies and the known biokinetic data of technetium compounds in man it was possible to calculate the radiation dose to the human foetus during isotope investigations of the mother.

Animals↗
PubMed1987

Sources and behavior of technetium in the environment.

Technetium is a man-made element produced in increasing amounts during the last decades. The chemical and physical properties of some technetium compounds are considered, and a discussion of possible source terms is included. Literature on the environmental behavior of technetium is reviewed to evaluate its transfer and equilibrium distribution in aquatic and terrestrial ecosystems. Considerable effort has been expended in the last years in order to understand the biogeochemical processes responsible for the long-term behavior of technetium in the environment and its transfer through food chains as well as to identify critical pathways of the long-lived radioisotope Tc-99 from the environment to man.

Environmental Pollution↗
PubMed2004

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↗
PubMed2000

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↗
PubMed2004

An in vitro study to compare 99mTc-stannous colloids and 99mTc-HMPAO for labelling human leukocytes.

AIM: Aim of the present study was to compare in vitro the labelling efficiency (LE) and cell viability (TBE) of autologous leukocytes labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO, and to evaluate the quantity and quality of spontaneously released (99m)Tc (SR) from labelled cells at several time points after labelling. METHODS: A total of 14 patients with different diseases and 18 normal subjects were included in this study. A blood sample was collected from each patient; purified autologous leukocytes were divided into 2 samples and labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO. LE was evaluated at the end of labelling and TBE and SR were evaluated at 10 min and 1 h, 2 h and 4 h after labelling. RESULTS: LE of (99m)Tc-SnF(2)-WBC was higher than (99m)Tc-HMPAO-WBC (61.2+/-18.7% and 43.3+/-11.3; p<0.0001) and we found an inverse correlation between blood glucose and labelling efficiency for both methods (p=0.02). Minimal differences were also observed between 2 methods after 10 min and 1 h, as far as the cell viability is concerned. The percentage of radioactivity spontaneously released from (99m)Tc-SnF(2)-WBC was significantly higher compared to (99m)Tc-HMPAO-WBC at each time point. Radioactivity released from labelled cells was predominantly (99m)Tc-SnF(2) and (99m)Tc-HMPAO with few free (99m)Tc (<20%). CONCLUSION: Both radiopharmaceuticals are not toxic for WBC. Labelling with (99m)Tc-SnF(2) give a higher LE than with (99m)Tc-HMPAO; however, radiolabelled colloids are more released from labelled cells over a period of 4 h. While (99m)Tc-HMPAO is physiological excreted into gastrointestinal tract, (99m)Tc-SnF(2) can be re-uptaken in vivo by reticulo-endothelial cells of liver and spleen. These findings suggest that (99m)Tc-SnF(2)-WBC might be better than (99m)Tc-HMPAO-WBC for studying inflammatory bowel diseases.

Cells, Cultured↗
PubMed1994

[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↗
PubMed1988

99mTc bone scanning agents--IV. Chemical characterization of 99mTc(Sn)-pyrophosphate complexes.

Various reaction mixtures for the preparation of 99Tc(Sn)-pyrophosphate were investigated by means of gel chromatography. All components were radioactively labeled. The most likely composition of the complexes, which also appear in "no carrier added" preparations, was determined. At pH 7 one complex is found with the composition TcPyp2. Two complexes are found at pH 4: TcPyp and TcPyp2. Further, at pH 7 a polymeric technetium compound is found not containing tin or pyrophosphate.

Bone and Bones↗
PubMed2005

Radiolabelling of egg meals for gastric emptying studies: a comparison of 99mTc sulfur and 99mTc stannous colloids.

OBJECTIVES: To establish whether 99mTc stannous (Tc-Sn) colloid is a suitable alternative to 99mTc sulfur (Tc-S) colloid for gastrointestinal studies, we compared the per cent binding to egg solids (%BS) and radiochemical purity (RCP) of both colloids in digesting media. METHODS: Egg white and yolk containing colloids were cooked separately and mashed. Samples of 4-5 g were digested over 2-3 h (37 degrees C) in excess simulated gastric juice (SGJ: 15 ml of 0.1 M HCl and 0.5 g.l-1 pepsin) or water, centrifuged, imaged with a gamma camera and the %BS computed. RCP was determined in aspirates taken from these preparations and from solutions of colloid added directly to SGJ. RESULTS: The %BS in egg white after 3 h in SGJ for both colloids were similar: Tc-Sn, 62+/-8 (n=12); Tc-S, 61+/-6 (n=8), but markedly lower than 95% (the often quoted literature value). Egg yolk was digested more rapidly than egg white: %BS after 2 h in SGJ for Tc-Sn colloid was 55+/-10 (n=5) in the yolk, compared to 77+/-4 (n=5) in the white (P<0.01). The RCP for Tc-S colloid alone in SGJ was >94% over 3 h but for Tc-Sn colloid was as low as 14%. For egg white, the RCP in SGJ was 91-96% for Tc-S and 80-91% for Tc-Sn. For egg yolk the RCPs in SGJ were similar for both colloids (>90%). The RCP in water digesting egg white or yolk containing either colloid was always lower than in the corresponding SGJ aspirates, indicating a leakage of small amounts of non-colloidal 99mTc. CONCLUSIONS: Although 99mTc-Sn almost completely dissociates in SGJ, once cooked in egg it is digested similarly to 99mTc-S. Variations in the size of digesting egg fragments and in SGJ composition can reconcile the lower %BS values obtained with previously reported higher results. 99mTc-Sn colloid cooked in egg appears suitable for gastrointestinal studies.

Eggs↗
PubMed2001

Significance of lymphoscintigraphic mapping with Tc-99m human serum albumin and tin colloid in sentinel lymph node biopsy in breast cancer.

Sentinel lymph node biopsy (SLNB) in breast cancer is considered in order to spare node-negative patients from axillary lymph node dissection. To assess the clinical significance of lymphoscintigraphic mapping in SLNB, we analyzed the lymphatic drain to the sentinel lymph nodes (SLNs) in terms of the pattern and direction of the hot spot. Twenty-three breast cancer patients were enrolled for SLNB. Before surgery, lymphoscintigraphic mapping of SLN was performed using Tc-99m human serum albumin (HSA) and tin colloids, and the hot spot was marked. The Tc-99m HSA and tin colloids were subcutaneously injected above the tumor and peritumor sites, respectively, and lymphoscintigraphic scanning was monitored every 5 to 10 min, for up to 2 h after injection. The SLN was identified using a combination of a blue dye, indigocalmine, and a gamma probe during surgery. The hot spot pattern and direction of the lymphatic drains were evaluated in 21 of 23 cases. Two cases did not have a hot spot. Single, double, and multiple hot spots were observed in 12 cases (52.1%), 8 cases (34.7%), and 1 case (4.3%), respectively. The positions of the hot spots were: axillary (n=17, 80.9%), axillary and sternal (n=3, 14.2%), and phrenic (n=1, 4.7%). The sensitivity and specificity rates in SLNB were 66.6% and 100%, respectively, and the overall predictive rate was 85.7%. Lymphoscintigraphy produced false negatives in three cases (33.3%), including one on the phrenic side. Lymphoscintigraphic mapping with Tc-99m HSA and tin colloids is useful for determining the SLN, and avoiding a false negative. The pattern and direction of the lymphatic drain to the SLN in scintigraphy need to be considered for the elimination of axillary lymph node dissection in node-negative patients with breast cancer.

Adult↗