Intraarticular injection of a Tin-117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects.

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin-117 m (117m Sn) colloid after intra-articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine-18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5-1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra-articular injection of 117m Sn colloid (92.5 MBq; 1-1.5 ml). Post-injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45-47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the 117m Sn activity was retained in the joint for 45-47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the 117m Sn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.

Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 µg/g creatinine or 20 µg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 µg/g creatinine) and France (0.51 and 2.28 µg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.

Development of in situ forming thermosensitive hydrogel for radiotherapy combined with chemotherapy in a mouse model of hepatocellular carcinoma.

This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide ((188)Re-Tin colloid) and a chemotherapeutic drug (liposomal doxorubicin). The thermosensitive PCL-PEG-PCL copolymer was designed to spontaneously undergo a sol-gel phase transition in response to temperature, remaining liquid at room temperature and rapidly forming a gel at body temperature. A scanning electron microscope was used to observe the microstructure of the fully loaded hydrogel. Release of radionuclide and doxorubicin from the hydrogel was slow, and the system tended to remain stable for at least 10 days. After the intratumoral administration of Lipo-Dox/(188)Re-Tin hydrogel in mice with hepatocellular carcinoma (HCC), its retention by the tumor, spatiotemporal distribution, and therapeutic effect were evaluated. The residence time in the tumor was significantly longer for (188)Re-Tin loaded hydrogel than for Na (188)Re perrhenate (Na (188)ReO4). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free (188)Re perrhenate ((188)ReO4) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/(188)Re-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either (188)Re-Tin hydrogel or Lipo-Dox hydrogel. Therefore, this injectable and biodegradable hydrogel may offer the advantage of focusing radiotherapy and chemotherapy locally to maximize their effects on hepatocellular carcinoma.

Tin and fluoride as anti-erosive agents in enamel and dentine in vitro.

OBJECTIVE: To investigate the efficacy of an experimental tin- and fluoride-containing mouth rinse on progression of erosion in enamel and dentine in vitro. MATERIAL AND METHODS: Human enamel and dentine specimens were subjected to a cyclic demineralization and remineralization procedure for 10 days, with six 5-min demineralization periods per day. Erosive demineralization was performed with 0.05 M citric acid (pH 2.3). Except in the negative control group, the specimens were treated for 2 min with mouth rinses after the first and sixth demineralizations. An experimental tin-containing fluoride mouth rinse [125 mg/kg F(-) (amine fluoride), 375 mg/kg F(-) (NaF), 800 mg/kg Sn(2+) (SnCl(2))] and an experimental sodium fluoride mouth rinse (500 mg/kg F(-)) were used (both pH 4.5). A commercially available, tin-containing mouth rinse served as a positive control (pH 4.2, 409 mg/kg Sn(2+), 250 mg/kg F(-)). Tissue loss was determined profilometrically. RESULTS: The highest tissue loss was found in the negative control group, in both enamel and dentine. In enamel, the NaF solution showed almost no effect. Both tin-containing solutions significantly reduced tissue loss (positive control: 65%; 800 mg/kg Sn(2+): 78%; both p ≤ 0.001 compared to negative control). In dentine all mouth rinses significantly reduced tissue loss (positive control: 43%; 800 mg/kg Sn(2+): 53%; NaF: 40%; all p ≤ 0.001 compared to negative control). CONCLUSIONS: In enamel, the efficacy of mouth rinses depended on the compound used; tin-containing preparations were notably effective. In dentine, however, reduction of substance loss was nearly the same in all treatment groups.

Radiation synovectomy using 188Re-tin colloid improves knee synovitis as shown by MRI in refractory rheumatoid arthritis.

BACKGROUND: Radiation synovectomy is a useful local treatment for patients with refractory synovitis. We previously demonstrated the efficacy and safety of Re-tin colloid for treating rheumatoid arthritis patients with refractory knee synovitis. This open-label, prospective controlled study investigates magnetic resonance imaging (MRI) changes as well as clinical response in knees after receiving different radioactivities of intra-articular Re-tin colloid. METHODS: Sixteen patients with rheumatoid arthritis refractory to intra-articular corticosteroid therapy were treated with intra-articular injection of Re-tin colloid (555 MBq in six patients, 740 MBq in five, and 925 MBq in five). Contralateral knees were used as controls. Treatment efficacy and safety were evaluated 1, 3 and 6 months later. We compared the changes of synovial thickening and joint effusion between baseline and 6 months. Synovial thickness was measured by gadolinium-enhanced MRI. RESULTS: Pain intensities on a visual analogue scale were significantly lower (median pain reduction, 78.9%; P=0.0001), joint swelling improved (median, -1.5; P=0.001), range of motion increased (median, 6 degrees , P=0.005), and joint tenderness decreased (median, -1; P=0.005) in treated knees after 6 months. The control knees did not show any significant clinical improvement. At 6 months after therapy, synovial thickening of treated knees improved in 87.5% of patients (P<0.001), and synovial thicknesses were significantly decreased in treated knees (P=0.0067). Furthermore, reduction in synovial thickness was most noticeable in the group treated with 925 MBq (P=0.007). No abnormalities in leukocyte or platelet counts, liver function tests, or urine analysis were observed. CONCLUSION: Radiation synovectomy using Re-tin colloid in refractory rheumatoid arthritis patients improved MRI findings as well as clinical parameters.

Synthesis and characterization of Sn(IV) complexes of lower rim 1,3-diacid derivative of calix[4]arene and their protective effects on tissue oxidative stress and essential metal concentration in lead exposed male Wistar rats.

The two Sn(IV) complexes synthesized using calix[4]arene-1,3-di-acid derivative were characterized by analytical, (1)H, (13)C and (119)Sn NMR, matrix assisted laser desorption ionization mass, and (119)Sn Mossbauer techniques and found that the complexes are tetranuclear possessing structurally two different types of tin centers. These complexes were evaluated for their protective value against blood and tissue oxidative stress in lead exposed male albino rats of Wistar strain. The results suggest that the two tin complexes significantly protect changes in lead induced biochemical variables indicative of heme synthesis pathway and exhibit only moderate effect on tissue oxidative stress. The beneficial effects could be attributed mainly to the ability of Sn(IV) complexes in preventing absorption of lead to the target sites/tissues.

Effect of Sn addition on the corrosion behavior of Ti-7Cu-Sn cast alloys for biomedical applications.

The aim of this study was to investigate the effects of Sn content on the microstructure and corrosion resistance of Ti7CuXSn (x=0-5 wt.%) samples. The corrosion tests were carried out in 0.9 wt.% NaCl solution at 25 °C. The electrochemical corrosion behavior of the Ti7CuXSn alloy samples was evaluated using potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS), and equivalent circuit analysis. The resulting impedance parameters and polarization curves showed that adding Sn improved the electrochemical corrosion behavior of the Ti7CuXSn alloy. The Ti7CuXSn alloy samples were composed of a dual-layer oxide consisting of an inner barrier layer and an outer porous layer.

Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.

We have reported that short-term treatment of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats with stannous chloride (SnCl2), which selectively depletes renal cytochrome P450, restores blood pressure to normal in young but not in adult SHR, and is without effect on blood pressure of either young or adult WKY rats. We report in the present study that chronic treatment with SnCl2, begun at age 5 weeks, prevented the development of hypertension in SHR over a period of 15 weeks at which time they were killed. Suspension of SnCl2 treatment after 8 weeks (i.e., at age 13 weeks) did not result in return of blood pressure to hypertensive levels in SHR. Age-matched WKY rats were not affected by tin treatment. These findings provide additional evidence that administration of tin, which stimulates heme oxygenase, thereby producing depletion of cytochrome P450, restores blood pressure to normal levels in SHR.

Effects of dietary tin on tin and calcium metabolism of adult males.

The effects of dietary tin on tin and calcium metabolism were determined in eight adult males. Subjects were fed mixed diets containing 0.11 mg tin daily (control diet) and 49.67 mg tin daily (test diet) for 20 days each in a cross-over design. The level of tin in the control diet was typical of the level of tin found in diets that contained only fresh and frozen foods; the level of tin in the test diet was typical of the amount of tin in diets that contained several servings of certain canned foods. Subjects apparently absorbed 3 and 50% of their dietary tin intake when fed the test and control diets, respectively. Subjects lost significantly more tin in their urine, but retained significantly more tin when fed the test diet rather than the control diet. The fecal and urinary losses and serum levels of calcium were not affected by the dietary treatments.

Effects of dietary tin on zinc, copper, iron, manganese, and magnesium metabolism of adult males.

The effects of dietary tin on zinc, copper, iron, manganese, and magnesium metabolism were determined in eight adult males. Subjects were fed mixed diets containing 0.11 mg tin daily (control diet) and 49.67 tin daily (test diet) in this 40-day study. The level of tin in the control diet was typical of the levels of tin found in diets that contain only fresh and frozen foods; the level of tin in the test diet was typical of the amount of tin in diets that contain 2 cups of certain canned foods. When subjects were fed the test diet they lost significantly more zinc (p less than 0.01) in their feces and significantly less zinc (p less than 0.05) in their urine. Subjects retained significantly less zinc (p less than 0.01) when fed the test diet rather than the control diet. The fecal and urinary losses of copper, iron, manganese, and magnesium were not significantly affected by the dietary treatments.

Percutaneous inoculation of lymph nodes.

Injections into rat lymph nodes are easily performed percutaneously, without the need for a skin incision, if the nodes are enlarged in advance. The requisite enlargement of the popliteal lymph node can be obtained in 2 or 3 weeks by a single injection of tin powder or other particulate material into the foot. This method may be especially useful when multiple intranodal inoculations are contemplated.

Labeling of red blood cells with Tc-99m after oral administration of SnCl2: concise communication.

In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl2, both in rats and human volunteers. Absorption of oral SnCl2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloride. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of 99mTcO4- in rats that were fed 5 mg of stannous chloride (3.13 mg Sn2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl2. We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m--such as the amount of orally administered SnCl2, the time of injection of radionuclide after oral SnCl2, and the optimum time for the imaging.

Antibody-targeted photolysis. Bacteriocidal effects of Sn (IV) chlorin e6-dextran-monoclonal antibody conjugates.

Antibody-targeted photolysis is a technique for damaging or killing cells using light and an antibody-bound photosensitizer. In the present study, immunoconjugates were constructed to selectively kill Pseudomonas aeruginosa bacteria using tin (IV) chlorin e6 which was linked to dextran and then bound to the carbohydrate moiety of a monoclonal antibody specific for Pseudomonas aeruginosa Fisher type I polysaccharide antigen. Killing of Pseudomonas during mid-log phase growth was shown to be dependent upon light dose with complete bacterial cell killing observed at an irradiation dose of 80 J/cm2. Individual components of the immunoconjugates (e.g., antibody or chlorin alone) showed no bacterial cytotoxicity and immunoconjugates constructed with nonbinding antibodies were also ineffective as cytotoxic agents. These studies demonstrate that killing of gram negative bacteria using photoradiation is feasible and suggest that this methodology may be applicable in treatment of infections in man.

Effect of multiple dental floss-SnF2 treatment on Streptococcus mutans in interproximal plaque.

Samples of dental plaque obtained from the interproximal tooth surfaces of seven young men showed considerable variation in the prevalence and anatomic site distribution of the potentially cariogenic microorganism S mutans. Multiple application of 10% SnF2 topical solution and saline solution delivered to interproximal test sites with dental floss were evaluated as short-term measures for eliminating S mutans from these surfaces. A greater overall reduction in the number of positive S mutans sites was observed for the SNF2-treated sites than the saline solution-treated sites. Long term studies are required to evaluate the effect of the treatments on the incidence of dental caries.

Some toxicological aspects of sttanous fluoride after ingestion as a clear precipitatefree solution compared to sodium fluoride.

Weanling rats were administered 20, 380, and 20,000 ppm F as clear precipitatefree SnF2 solutions. Equivalent ppm F as NaF solution was similarly administered for comparison. The rats were autopsied at the end of the study for histological examination of kidney, liver, and incisors. The pathognomonic manifestations were correlated with the plasma F levels.

Response of L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells to various metal cations.

Recent data suggest that under certain conditions, various metal cations are released from dental alloys. These ions may produce adverse effects in various cell types in vivo. In this study, the cytopathogenic effects of 13 metal cations on murine L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells were analyzed in vitro. Several metal cations (dose range, from 0.0033 to 1.0 mmol/L) were found to induce dose-dependent inhibition of 3H-thymidine incorporation into cultured fibroblasts. The rank order of potency (lowest observed effect level, LOEL) for L-929 fibroblasts was: Ag+ > Pt4+ > Co2+ > In3+ > Ga3+ > Au3+ > Cu2+ > Ni2+ > Zn2+ > Pd2+ > Mo5+ > Sn2+ > Cr2+. A similar rank order of potency was obtained for primary human gingival fibroblasts: Pt4+ > Ag+ > Au3+ > In3+ > Ga3+ > Ni2+ > Co2+ > Zn2+ > Cu2+ > Cr2+ > Pd2+ > Mo5+ > Sn2+. In primary human mast cells, Ag+ and Au3+ caused dose-dependent toxic histamine release, whereas the other metal cations were ineffective over the dose range tested. To investigate the mechanism of metal cation-induced effects, we performed DNA as well as electron microscopic analyses on cultured fibroblasts. Both the DNA pattern and the ultrastructure of L-929 cells and gingival fibroblasts after exposure to cytopathogenic metal cations revealed signs of necrosis but no signs of apoptosis. Together, our data provide evidence that various metal cations produce dose-dependent cytopathogenic effects in distinct cell types, including human gingival fibroblasts and human tissue mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

[The distribution of Sn2+ after application as a complex (author's transl)]. / Das Verhalten von Sn2+ nach seiner Applikation als Komplexsalz

On animal experiments was shown that Sn2+ after i.v. application with 113Sn as radioactiv indicator was deposited in the skeleton. Experiments were done with citrat-, tartrat-, pyrophosphat-, phosphat- and Sn2+/HCl-complexes. The importance of the results for the use of Sn2+-solutions in Nuclear Medicine for men are discussed.

[Modified biological behaviour of 99mTc-pertechnetate in man as a result of a preceeding administration of tin (tin effect) (author's transl)]. / Verändertes biologisches Verhalten zon 99mTc-Pertechnetat nach vorangegangener Zinngabe ("Zinn-Effekt") am Menschen.

An increased image of blood-filled spaces (Plexus choriodeus, Sinus transversus) was observed in 99mTc-pertechnetate scintigraphy when it had been preceded by the administration of tin (e.g. of 99mTc-Sn-diphosphonate). We have called this behaviour the "tin effect". In vitro studies demonstrated binding of about 80% of the administered activity in the blood with a biological half-life of about 44 hr and an effective half-life of about 5.3 hr. 95% of the blood activity was bound to red cells and 5% to plasma. This resulted in an increased radiation dose to the bone marrow of about 530 mrad/mCi 99mTc-pertechnetate (following tin). The extent of the tin effect decreased with the length of the interval between tin and 99mTc-pertechnetate administration. Because of the tin effect 99mTc-DTPA or 99mTc-citrate should be used for brain scintigraphy if this has to be performed within the first 5 or 7 days following a bone scintigraphy with a tin-containing radiopharmaceutical. The "tin effect" might be taken advantages of when labelling red cells and imaging vascular spaces.

Evaluation of a simpler technique for in-vivo labelling of red blood cells with 99mTc.

The efficiency of labelling red blood cells with intravenously administered 99mTcO4, by prior oral administration of stannous chloride dihydrate, has been evaluated. Optimum labelling occurred 1 hr after the oral dose of 200 mg of SnCl2.2 H2O and 20 min after the intravenous injection of 99mTcO4. The mechanism of labelling has been shown to be diffusion of 99Tc through the cell membrane followed by binding to haemoglobin in the presence of reducing agent. The in-vivo labelling technique has been found to be useful for the diagnosis of an abdominal mass and for static perfusion studies.

Metallic tin-induced lymphadenopathy in rat strains and hybrids.

Metallic tin powder, injected into Lewis rats obtained from three different sources, caused enlargement of the regional draining lymph nodes. The histopathology featured epithelioid cell granulomas around phagocytosed particles of tin and an intense hyperplasia of plasma cells. The same material injected into August rats enlarged the lymph nodes but the enlargement was caused by granulomas without a major concomitant plasma cell response. In most other strains, tin produced less lymph node enlargement and the plasma cell response was minimal. However, F1 hybrids of Lewis rats with either the August, Brown-Norway (BN), or Dark Agouti (DA) strains developed plasma cell hyperplasia similar to that seen in the parental Lewis strain. The response to tin was the same whether the tin was injected into the feet or into the peritoneal cavity. Thus, the lymph node response to metallic tin varied from a slight, banal response to insoluble foreign particles, to an exuberant granulomatous hyperplasia, to an intense plasmacellular hyperplasia, depending on the genetic characteristics of the subjects.