Colonic transit scintigraphy labeled activated charcoal compared with ion exchange pellets

Scintigraphic measurement of colonic transit is currently performed by delivering 111In ion exchange resin pellets to the colon in a methacrylate-coated capsule. However, use of this method is constrained by the need for an investigational drug permit. We have demonstrated previously optimal adsorption in vitro of commonly used radioisotopes (e.g., 99mTc or 111In) to activated charcoal in milieus that mimicked gastric and small intestinal content. The aim of this study was to compare the transit profiles of radioactive activated charcoal and resin pellets delivered to the colon in the same methacrylate-coated capsule. METHODS: In 10 healthy volunteers, we compared the colonic transit profiles over 32 hr of simultaneously administered resin pellets labeled with 111In and activated charcoal mixed with 99mTc-diethylenetriaminepentaacetic acid. Transit was summarized as the geometric center (weighted average of counts) in the colon at each scanning period. RESULTS: Colonic transit profiles were virtually identical with the two markers, with less than 0.1 geometric center unit differences in the transit profiles over the 32-hr periods. CONCLUSION: Activated charcoal is a suitable alternative to resin pellets when delivered in a methacrylate-coated, delayed-release capsule to the colon for measurement of transit by scintigraphy.     

Imaging experimental osteomyelitis using radiolabeled liposomes

We evaluated radiolabeled liposomes (liposomes labeled both with 99mTc and 111In) for the early detection of osteomyelitis in an experimental model. METHODS: Liposomes, containing 5% polyethylene glycol-distearoyl phosphatidylethanolamine with encapsulated glutathione and deferoxamine, were prepared and labeled with 99mTc and 111In by a previously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and Staphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi 99mTc and 75-125 microCi 111In), 99mTc-methylene diphosphonate (MDP) (3-5 mCi) and 67Ga-citrate (500 microCi), were performed starting at the third day after injection. Each radionuclide study was separated by at least 2 days. The animals also underwent radiography of the lower extremities. The animals were then killed and the infected tibia was excised for histopathology. RESULTS: For interpreting relative efficacy of individual radiopharmaceuticals, only animals showing positive histopathological findings (n = 9) were considered. Radiographs (Days 12, 13) were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though the lesion could be delineated as early as 8 hr postinjection in the 99MTc window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained at 48 hr in the 111In window. Three-phase 99mTc-MDP scan (Day 7) was positive in only 5 rabbits with 3 hr T/NT of 1.6 +/- 0.23. Galium-67-citrate images (Days 9-11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74 +/- 0.24. These results show liposomes are better than 99mTc-MDP for imaging bone infection. Given the early localization and better quality of the images, radiolabeled liposomes also exhibited advantages over 67Ga-citrate for detection of acute osteomyelitis.     

Uptake by rat liver and intracellular fate of plasmid DNA complexed with poly-L-lysine or poly-D-lysine

Adding normal saline (NS) separately before 99Tcm-sodium pertechnetate to MDP cold kits has been shown to reduce substantially the radiation dose to the hand. A similar dose reduction will probably prove to be valid with the preparation of most other 99Tcm-labelled radiopharmaceuticals. However, it is unknown how this altered reconstitution procedure may affect the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals. We have evaluated the effects on the labelling efficiency and in vitro stability of 99Tcm-labelled MDP, mertiatide and sestamibi reconstituted with three different methods: adding normal saline before 99Tcm activity (NS/Tc); adding 99Tcm activity before normal saline (Tc/NS); and the standard reconstitution method of adding both 99Tcm activity and normal saline together. The labelling efficiency and in vitro stability were evaluated by measuring the radiochemical purity of each radiopharmaceutical tested at 0, 1, 3, 6, 12 (except 99Tcm-MDP) and 24 h after reconstitution. For 99Tc-mertiatide, there was a very slight difference in the labelling efficiency, mostly due to the Tc/NS method being approximately 0.29% lower across time post-reconstitution than the standard method. For 99Tcm-labelled MDP and sestamibi, there were no differences between the three methods in terms of labelling efficiency and in vitro stability. In conclusion, both alternative methods (i.e. NS/Tc and Tc/NS) appear not to have any detrimental effect on the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals that we tested. However, of the two alternative kit reconstitution methods, we recommend the NS/Tc method, since it may reduce the hand radiation dose.     

Left ventricular shape analysis from three-dimensional echocardiograms

Cystic fibrosis patients require pancreatic enzyme supplements to aid food digestion. It is suspected that incorrect delivery of this enzyme may result in both significant malabsorption and the development of strictures in the proximal colon caused by the high-dose supplement reaching this region before the food. Investigations into the drug's delivery were performed using dual-isotope imaging; a method was developed to directly label the enteric-coated enzyme pellets with 111In, re-applying the enteric coating afterwards, and this was then ingested with a pancake meal labelled with 99Tcm-tin colloid. Consecutive image data, acquired over a period of > or = 4 h using a dual-headed gamma camera, were analysed to assess intestinal transit. In-vitro stability checks on these labelling techniques were encouraging, showing < 2% 99Tcm and < 7% 111In elution over 90 min in hydrochloric acid. In 5 of the 12 patients studied to date, the pellets were seen to pass through significantly faster than the food, with a mean difference in 50% gastric emptying time of greater than 93 min. The mean absolute difference in emptying time for all 12 patients was > 67 min. Thus, a technique has been developed to effectively radiolabel pancreatic enzyme pellets, and analysis of dual-isotope images using this preparation, together with radiolabelled solid food, has demonstrated significant differences in the transit of these two substances through the gastrointestinal tract of some cystic fibrosis patients.     

99mTc-citrate versus 67Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with 99mTc with an efficiency of > 99%. The biodistribution of 99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to 67Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 +/- 1.92 (3 h) for 99mTc-citrate and 4.76 +/- 2.04 (4 h) for 67Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of 99mTc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 +/- 1.29 (3 h) and 6.47 +/- 3.71 (24 h) for 99mTc- and 67Ga-citrate, respectively. The blood clearance curve of 99mTc-citrate in rabbits was biexponential with a fast (T1/2 = 36 min) and a slow (T1/2 = 18 h) component, compared to mono-exponential clearance of 67Ga-citrate (T1/2 = 23 h). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 +/- 0.81 and 4.95 +/- 2.56 for 99mTc-citrate and 99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that 99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to 67Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Charge and nature of technetium species produced in the reduction of pertechnetate by stannous ion

By using a cation-exchange distribution technique, the net charge of the technetium species produced in the reduction of pertechnetate by stannous ion at ph less than or equal to 2 had been determined to be + 2. The species carrying this charge is either the dihydroxy technetate (Tc(OH)2(2)+) ion or the oxotechnetate (TcO2+) ion. These species are hydrolysed to technetium dioxide dihydrate (TcO2 - 2H2O) at higher pH.The advantage of the ion-exchange distribution technique for these studies is that they can be done with carrier-free technetium rather than at the high concentrations required for the more conventional methods of ion-charge determination. The results, therefore, are more likely to be applicable to the situation existing in the routine preparation of Tc-99m radiopharmaceuticals.     

特种离子交换树脂从钼酸铵溶液中深度分离钒

研究了采用特种阴离子交换树脂分离钼酸铵溶液中的钒。首先,采用静态吸附考察了料液平衡pH、料液钼浓度、氯离子浓度、吸附时间等因素对分离过程的影响;然后,进行动态交换实验,采用料液pH=8.01,接触时间60 min,处理料液为67倍树脂体积时,除钒率达到99.83%,树脂对V2O5工作交换容量为78.7 g/L,钒钼分离系数达到22522.9;用2 mol/L的NaOH溶液可以对负载树脂实现彻底解析。     

石煤浸出液离子交换法提钒的研究

选择了几种离子交换树脂,对石煤酸浸含钒液在不同条件下进行离子交换实验.结果表明:采用离子交换法能够很好地除去浸出液中大部分杂质,并能使钒得到富集;不同树脂对钒的吸附均受吸附时间、溶液pH值等实验条件的影响,不同解吸剂与解吸时间也会影响树脂解吸的效果;1#树脂吸附率在4h左右可达到99%的最大吸附能力,选择合适的解吸剂可在4h内使钒的解吸率达到95%以上;解吸液经过净化,沉钒,煅烧后得到的五氧化二钒纯度在99%以上.     

树脂对稀土冶炼废水氨氮的吸附及动力学研究

利用离子交换树脂法对稀土冶炼废水中氨氮进行处理,考察树脂用量、时间、温度及pH等因素的影响,并进行动力学研究实验.实验结果表明：树脂用量增加、时间增加、温度升高、pH值升高均有利于提高离子交换容量;D113树脂对氨氮的离子交换过程符合二级动力学方程.     

Labelled Stealth liposomes in experimental infection: an alternative to leukocyte scintigraphy?

Indium-111 (111In) and technetium-99m (99Tcm) Stealth liposomes were compared with 111In- and 99Tcm-labelled white blood cells (WBC) in experimental infection in a rabbit model. Preformed polyethylene glycol-coated liposomes and separated WBC were radiolabelled with either 111In-oxine or 99Tcm-hexamethylpropyleneamine oxime (99TcM-HMPAO). After the intravenous administration of one of the four radiopharmaceuticals to rabbits with focal Staphylococcus aureus infection, scintigraphic images were recorded at various time points post-injection and the biodistribution of the radiopharmaceuticals was determined. At 4 h post-injection, uptake of 111In-WBC in the abscess was significantly higher than that of the three other products. AT later time points, 111In-WBC, 111In-liposome and 99Tcm-liposome uptake in the abscess were similar. In contrast, a 20 h post-injection, uptake of 99Tcm-WBC was significantly lower. The abscess-to-background ratios showed a similar pattern to the absolute abscess uptake: initial high values for 111In-WBC, a more gradual increase over time of the liposome preparations to the level of 111In-WBC and persistently low values for 99Tcm-WBC. Clearance from the blood of both labelled WBC preparations was significantly faster and splenic uptake significantly higher compared with those of the labelled liposomes. In conclusion, given the similar in vivo characteristics of labelled liposomes and labelled WBC, labelled liposomes may be an attractive replacement for labelled WBC, providing a continuously available, high-quality, 99Tcm-labelled radiopharmaceutical that can be prepared easily without any need to handle blood.     

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.     

Colonic transit time assessed by 67 Ga-citrate in a case-series of patients with recto-sigmoid adenomas

One plausible mechanism by which dietary factors may influence colorectal carcinogenesis is through their effect on intestinal transit time. This study examined colonic transit by means of oral 67Ga-citrate in a case-series of patients who had developed recto-sigmoid adenoma. Adenoma patients had a significantly shorter transit time than constipated patients (P = 0.01) and our results also suggest (but do not show conclusively) that colonic transit in adenoma patients is similar to that of normal controls. Although these findings require confirmation from a larger study, they raise the hypothesis that colonic transit times are not delayed in patients who harbour recto-sigmoid adenomas.     

Radionuclide diagnosis of local inflammation in patients with rheumatoid arthritis

Radionuclide scintigraphy with osteotropic radiopharmaceuticals labelled 99Tc proved highly sensitive in assessment of local inflammation. Osteoscintigraphy allows detection of preclinical and pre-x-ray lesions in the joints in RA and assessment of the treatment efficacy. Characteristic signs of the radionuclide distribution and accumulation can serve as a prompt in differential diagnosis of RA, DOA, reactive and gouty arthritis.     

Intragastric distribution of ion-exchange resins: a drug delivery system for the topical treatment of the gastric mucosa

Previous studies by this group on freeze-dried oral dosage forms containing finely-divided ion-exchange resins revealed prolonged gastric residence and uniform distribution within the stomach. The present study was carried out to ascertain whether this was due to freeze-drying, properties of the radiolabelled ionic exchange resin, or the small dosing volume used. 99mTc-labelled cholestyramine resin was administered in two dosage forms, a freeze-dried tablet which dissolved in the oral cavity (orally dissolving tablet; ODT) and a 1.5 mL aqueous suspension. Two resin particle sizes (20-40 and 90-125 microns) were studied. Oesophageal transit and intragastric distribution and residence were followed by gamma scintigraphy. In a second study, in six subjects, gastric emptying of the water-soluble fraction of the ODT and 1.5 mL of water, was measured using 99mTc diethylenetriaminepentaacetic acid. Oesophageal transit of a water-soluble marker and resin in suspension was rapid, but the transit of the resin in the ODTs was significantly prolonged. Regardless of particle size or dosage form, the resin was evenly distributed throughout the stomach with 20-25% remaining for 5.5 h. In contrast, the water-soluble marker cleared from the stomach rapidly from both dosage forms. We suggest that oral dose forms containing finely-divided ion-exchange resins may form a useful system for topical treatment of the gastric mucosa, for example in targeting to Helicobacter pylori infection.     

The influence of haemoperfusion on haemostasis and cellular constituents of the blood in the treatment of intoxications: a comparative study of three types of columns (Haemocol, Amberlite XAD-4, Gambro Adsorba 300 C)

The influence of haemoperfusion on blood-coagulation and cellular constituents of the blood was studied in three groups of patients. In four patients haemoperfusion was performed using a column containing acrylic-hydrogel coated activated charcoal (Haemocol), in five patients with a column containing uncoated XAD-4 nonionic polystyrene resin (Amberlite) and in five patients with a column containing cellulose coated activated charcoal (Gambro Adsorba 300 C). Perfusion was performed during 4 h with a flow of 300 ml/min. Before the start, 2 h after the start, at the end and 2 h after the end of the perfusion the haemoglobin concentration, haematocrit, leucocyte number, differential white cell count, thrombocyte number and heparin concentration were measured. Before the start and 2 h after the end prothrombin time, thrombin time, partial thromboplastin time, reptilase time, fibrinogen, prothrombin, factors V, VII, X, antithrombin III, bleeding time (Ivy), ethanol gelation test, fibrin split products and plasminogen were measured. The following conclusions can be drawn: haemoperfusion per se causes haemodilution; polystyrene resin causes in some patients a temporary reduction of the leucocyte number during haemoperfusion; polystyrene resin causes a significant reduction of thrombocyte number compared to coated activated charcoal; polystyrene resin and to a lesser extent acrylic-hydrogel-coated activated charcoal causes in some patients a prolongation of bleeding time probably by inducing alteration of thrombocyte function caused by release; polystyrene resin and probably also acrylic-hydrogel-coated activated charcoal causes an increased fibrinolytic activity without signs of disseminated intravascular coagulation.     

Dynamic distribution and dosimetric evaluation of human non-specific immunoglobulin G labelled with 111In or 99Tcm

This study presents data on the dynamic distribution and dosimetry of 111In- and 99Tcm-labelled human non-specific immunoglobulin G (IgG), two recently developed radiopharmaceuticals for the detection of infection and inflammation. Five healthy volunteers were injected with 20-75 MBq 111In-IgG and seven patients were injected with 740 MBq 99Tcm-hydrazinonicotinamide derivative (HYNIC)-IgG. Blood samples, urine and feces were collected. Whole-body gamma camera imaging studies were performed. The activity in source organs was quantified using the conjugate view counting method and a partial background subtraction technique. Dosimetric calculations were performed using the MIRD technique. For 111In-IgG, the mean biological half-times in the blood were 0.90 and 46 h for the a- and b-phase, respectively. For 99Tcm-HYNIC-IgG, these half times were 0.46 and 45 h. For 111In-IgG, the mean cumulative urinary excretion in the first 48 h was 18% of the injected dose, while excretion in the feces was less than 2% of the injected dose. For 99Tcm-HYNIC-IgG, the whole-body retention was always 100% up to 24 h. The mean absorbed doses in the liver, spleen, kidneys, red marrow and testes from 111In-IgG were 0.8, 0.7, 1.2, 0.3 and 0.4 mGy MBq-1 respectively. The mean absorbed doses for 99Tcm-HYNIC-IgG to these organs were 16, 24, 15, 10 and 22 mu Gy MBq-1 respectively. The mean effective dose was 0.25 mSv MBq-1 and 8.4 mu Sv MBq-1 for 111In-IgG and 99Tcm-HYNIC-IgG respectively. In conclusion, the radiation absorbed doses for both 111In-IgG and 99Tcm-HYNIC-IgG are low and, therefore, these radiopharmaceuticals can be administered safely from a radiation risk perspective.     

Comparative drug adsorption by activated charcoal

Comparative in vitro studies were carried out to determine the adsorption characteristics of 12 drugs on activated charcoal. At pH 1.3 and 37 degrees, the adsorption capacity of activated charcoal (milligrams per gram of charcoal) was: aspirin, 262; glutethimide, 252; methaqualone, 179; chlordiazepoxide, 157; propoxyphene napsylate, 137; diazepam, 136; amitriptyline, 133; propoxyphene hydrochloride, 127; secobarbital, 124, pentobarbital, 103; phenobarbital, 70; and amobarbital, 51. The adsorption of the weak acids was most markedly decreased at pH 10.8. In patients, actual drug adsorption probably is lower than these maxima because of the presence of mucus, bile salts, and other drugs. In patients investing large amounts of poorly adsorbed drugs, activated charcoal would not be helpful.     

Relevance of biophysical concepts in the scintigraphic detection of gastrointestinal leaks

The application of some physical concepts is described to explain the inherent insensitivity of 99Tc(m)-red blood cell (RBC) and 99Tc(m)-human serum albumin (HSA) in the detection of gastrointestinal bleeding and protein-losing enteropathy (PLE), respectively. Inferences drawn from the laws of radioactive decay, partition physics, hydrodynamics and electrostatic forces have been used to suggest that the clearance pattern, size and charge of radiopharmaceuticals, and the viscosity of the medium, affect the sensitivity of these tests. As the outflow from gastrointestinal lesions is non-specific, other labelled macromolecules can be used instead of RBCs or HSA. Based on biophysical concepts, we suggest that chargeless macromolecules in the size range 5-50 nm are superior to the conventional agents used for this purpose.     

电容去离子技术分离石煤酸浸液中的钒和铝

采用一种新兴吸附技术—电容去离子技术(CDI),利用活性炭/离子交换树脂复合电极去除石煤空白焙烧—硫酸浸出液中的铝,考察了各工艺条件对钒、铝分离因数的影响。结果表明,当施加电压为2.0V、进料流量25mL/min、溶液初始pH 0.75、电极间距9mm时,对酸浸液中的铝的吸附量为422.4mg/g,钒、铝分离因数为28.3,钒、铝分离效果显著。     

离子交换法处理氰化贫液中铜的工艺及动力学

用201×7离子交换树脂处理黄金氰化贫液的高含量铜,研究了树脂吸附铜的工艺和动力学,考察了温度、pH、液固比和时间对吸附的影响。结果表明,该树脂能有效吸附氰化贫液中的铜。温度和pH对吸附性能影响不大,降低液固比能提高吸附效果;在1.0h后吸附趋于饱和,吸附过程符合一级动力学模型。