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Evaluation of (111) indium-labeled autologous leukocyte scintigraphy for the diagnosis of chronic osteomyelitis in patients with grade IV pressure ulcers, as compared with a standard diagnostic protocol.

Diagnosing osteomyelitis in patients with pressure ulcers is complicated by overlying soft-tissue inflammation and reactive bone formation. We set out to evaluate the efficacy of indium scanning in the diagnosis of chronic osteomyelitis in spinal-cord-injury patients with grade IV pressure ulcers. The goal was to estimate the sensitivity and specificity of indium scanning as compared with diagnostic modalities previously evaluated by the principal investigator. Our method was a retrospective chart review of cases at a university hospital. Eleven patients with pressure sores and suspected chronic osteomyelitis underwent indium scanning. The results were compared with ostectomy specimens taken at the time of reconstructive surgery and/or bone biopsy. The sensitivity and specificity were 100% and 50%, respectively. Indium scanning appears to be more sensitive than specific. These data suggest that the value of indium scanning may primarily be to rule out osteomyelitis and not as a primary diagnostic modality.

Aged↗

Indium chloride scintigraphy: an index of severity in patients with aplastic anaemia.

[111In]Indium chloride scans of the bone marrow were performed in 22 patients with idiopathic aplastic anaemia before therapeutic intervention. In 20 patients there was a marked reduction in the uptake of indium chloride by the marrow, and in two patients the uptake of indium chloride was normal. Nineteen of the 20 patients with reduced marrow uptake of indium chloride, who underwent bone marrow transplantation, died or failed to improve. One of the two patients with normal scans improved and the other has remained stable. Four patients studied both pre and post successful bone marrow transplantation had minimal marrow uptake before transplantation and normal scans after transplantation. Failure of indium-111 choride marrow uptake correlates with poor prognosis in idiopathic aplastic anaemia.

Adult↗

Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction.

The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.

Animals↗

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab.

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.

Animals↗

Indium-granulocyte scanning in the painful prosthetic joint.

The value of indium-111-labeled granulocyte scanning to determine the presence of infection was assessed in 50 prosthetic joints (41 of which were painful) in 40 patients. Granulocytes were obtained from the patients' blood and labeled in plasma with indium 111 tropolonate. Abnormal accumulation of indium 111 in the region of the prosthesis was noted. Proven infection occurred in 11 prostheses, and all of the infections were detected by indium-111-labeled granulocyte scanning. Nineteen were not infected (including nine asymptomatic controls) and only two produced false-positive scans. This represents a specificity of 89.5%, sensitivity of 100%, and overall accuracy of 93.2%. These results compare favorably with plain radiography. There was no radiologic evidence of infection in three of the infected prostheses, and 10 of the noninfected prostheses had some radiologic features that suggested sepsis. We conclude that indium-granulocyte scanning can reliably detect or exclude infection in painful prosthetic joints and should prove useful in clinical management.

Granulocytes↗

The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population.

Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients.

Adult↗

Limitations of indium leukocyte imaging for the diagnosis of spine infections.

The usefulness of indium-111 white blood cell (WBC) scintigraphy in the detection of spine sepsis was studied in 22 patients who had open or percutaneous biopsies for microbiologic diagnosis. The indium images in 18 patients with vertebral infection were falsely negative in 15 (83%) and truly positive in 3 (17%). All four patients with negative cultures and histology had true-negative scans. The indium-111 WBC imaging results yielded a sensitivity of 17%, a specificity of 100%, and an accuracy rate of 31%. Prior antibiotic therapy was correlated with a high incidence of false-negative scans and photon-deficient indium-111 WBC uptake. The usefulness of indium-111 WBC scintigraphy for the diagnosis of vertebral infection may be limited to those patients who have not been treated with antibiotics previously.

Anti-Bacterial Agents↗

Bone scan: indium-WBC correlation in the diagnosis of osteomyelitis of the foot.

A retrospective study was performed of 20 podiatric cases using technetium-99m methylene diphosphonate three-phase bone scans along with indium-111 oxine leukocyte scans, as needed, to determine the presence and extent of osteomyelitis of the foot. Using criteria developed at our institution, the authors attempt to provide a mechanism to make a reliable diagnosis for osteomyelitis that has been supported by surgical/pathologic confirmation of long-term clinical follow-up. The sensitivity, using bone scans alone, was 100%, and specificity was 47%. Correlating bone and indium-111 leukocyte scans yielded a sensitivity of 100% with a specificity raised to 81%. Indium-111 leukocyte scans were used in 40% of cases when a definitive diagnosis for osteomyelitis could not be made on the basis of the three-phase bone scan or clinical presentation alone. Indium-111 leukocyte scans were also helpful in delineating the extent of the disease process. The authors present a standard technique for a 5-hour delayed imaging in the three-phase bone scan, as well as marking the foot in the indium-111 leukocyte scan with three routine views obtained for each imaging procedure, to ensure clinical accuracy.

Adult↗

Diagnosis of infection by preoperative scintigraphy with indium-labeled white blood cells.

Scintigraphy with indium-labeled white blood cells has been reported to be sensitive and specific in the diagnosis of low-grade sepsis of the musculoskeletal system. We reviewed the records of fifty patients who had suspected osteomyelitis or suspected infection about a total joint prosthesis and who underwent scintigraphy with technetium-99m methylene diphosphonate and scintigraphy with indium-111 oxine-labeled white blood cells before an open surgical procedure. Any patient who received preoperative antibiotics was not included in the study. For all of the patients, gram-stain examination of smears, evaluation of a culture of material from the operative site, and histological examination were done. The patients were divided into two groups. Group I was composed of twenty-four patients, each of whom had a prosthesis in place and complained of pain. Group II was composed of twenty-six patients for whom a diagnosis of chronic osteomyelitis had to be considered. With the indium scans alone, there was only one false-negative result (in Group II), but there were eighteen false-positive results (eight patients in Group II and ten patients in Group I). Although scintigraphy with indium-labeled white blood cells is quite sensitive, it is not specific in detecting chronic osteomyelitis; a negative scan should be considered highly suggestive that osteomyelitis is not present. Specificity can be increased by interpreting the indium scan in conjunction with the technetium scan.

Adult↗

The indium-113m-transferrin complex as an indicator of serotonin-induced vascular changes in the golden hamster lung.

In order to measure experimentally-induced lung microvascular permeability changes in small laboratory animals, a method using the radioactive indium-113m-transferrin complex as a macromolecular tracer was adopted for a model of anesthetized hamsters. Serotonin or saline were given either systemically (intravenously) or locally (intratracheally). The effects were studied with arterial blood pressure recordings, wet-dry weight determinations of lung tissue and in vitro gamma scintillation of the lungs. Intravenous injections of serotonin (100 resp 400 nmol/kg b.w.) reduced the lung content of indium-113m with a maximum of 74%, intratracheal instillations of serotonin (100, 400, greater than 4000 nmol/kg b.w.) reduced the indium-113m content ranging from 48% to 71%. Saline intratracheal instillation alone decreased indium-113m content by 53%. In all animals receiving serotonin there were decreases in blood pressure which was also the case, but to a lesser extent, in the animals receiving saline intratracheally. The water content of the lungs was not significantly affected in any group. We conclude that the indium-113m transferrin macromolecular tracer complex is a reproducible method for measuring vascular events. The results give additional proof that serotonin administered intravenously or intratracheally does not increase microvascular macromolecular permeability in the lung, but rather acts as a vessel constrictor and/or increases transmural pressure.

Animals↗

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study.

We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracy was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.

Adolescent↗

Indium-111-labeled leukocytes for the localization of abscesses: preparation, analysis, tissue distribution, and comparison with gallium-67 citrate in dogs.

Leukocytes have been labeled with indium-111-8-hydroxyquinoline complex. Seventy-five to 85 per cent of the initial activity has been obtained in the complex form of which 75 to 95 per cent is incorportaed with leukocytes. The polymophonuclear leukocytes are predominantly labeled, and the label has been found stable for at least 27 hours after invivo administration. The radioactivity clears from the circulating blood with a half time of 8 to 9-hours and accumulates in normal liver and spleen and in experimentally induced abscesses. The cells which have been labeled and damaged by heat concentrate mainly in the lungs. The in vivo distribution of the indium-111 labeled cells has been compared with the gallium-67 administered as citrate. The abscess to blood ratios of the indium-111 activity varied between 35 to 117, compared to 1.2 to 8 of the gallium-67. The abscess to liver, spleen, and kidney ratios are several fold higher with indium-111 leukocytes than with gallium=67 citrate. These results plus the suitable physical characteristics of indium-111 make the labeled leukocytes a better agent for the localization of abscesses.

Abscess↗

Location and activity of ulcerative and Crohn's colitis by indium 111 leukocyte scan. A prospective comparison study.

A prospective blinded study comparing the indium 111 leukocyte scan to barium enema, colonoscopy, or surgery or a combination of these, was carried out in 15 patients (10 with active ulcerative colitis and 5 with active Crohn's colitis). Correlation of disease location to colonic regions between indium scan and other diagnostic studies was excellent in 11 instances, good in 2, and poor in 3. In 2 of the 3 studies where major disagreement occurred, the comparative barium enema was performed greater than 2 mo after the indium scan. Disease activity, estimated by the intensity of radionuclide uptake, was compared to clinical disease activity assessed by the Crohn's Disease Activity Index for both forms of colitis. The relative degree of inflammation estimated by the indium scan correlated well with the independent clinical assessment (correlation coefficient = 0.81). The indium 111 leukocyte scan appears to be an accurate, noninvasive method for assessing the extent and the severity of the inflammation in patients with acute ulcerative or Crohn's colitis.

Adolescent↗

Measurement of high dose rates by photon activation of indium foils.

Photon activation of indium foils is proposed as a dosimetry technique for high dose rate measurements in a 60Co irradiation facility. The irradiated indium nuclei may be raised to its metastable isomers of 113mIn and 115mIn. The isomer 115mIn, with appreciable induced radioactivity, was selected for dose-rate measurements. Based on the photon flux distribution and the derived dose rates, which were simulated by the MCNP code, the dependence of dose rate measurement sensitivity of indium foils with respect to photon energy at various irradiation distances is described. For practical uses, the radioactivity of 115mIn was linearly related to the dose rate response at the specified irradiation positions. By comparing with a calibrated dosimetry system, the measurement deviation of the indium dosimeter, over dose rates ranging from 10 to 10(4) Gy/h, was evaluated and exhibited an uncertainty of +/- 7%. Other related characteristics including measurement sensitivity and range, linearity with respect to the variation of dose rate, and limitations of the indium dosimeter were evaluated to justify it as an alternative for monitoring dose rate in an irradiation field.

Journal Article↗

Gallium and indium hydrazides. Molecular and electronic structure of In[N(SiMe3)NMe2]3 and related compounds.

Gallium and indium hydrazides, Ga[N(SiMe(3))NMe(2)](3) (1) and In[N(SiMe(3))NMe(2)](3) (2), were synthesized from the reactions of metal chlorides and Li[N(SiMe(3))NMe(2)]. Single crystal X-ray crystallographic analysis revealed that compound 2 was monomeric with trigonal planar geometries on the indium and the indium-bonded nitrogen atoms. The average In[bond]N distance of 2.078(3) A and the N[bond]In[bond]N[bond]N dihedral angles did not provide clear structural evidence of In[bond]N pi-bonding. The electronic absorption spectra of the indium hydrazido complex revealed transitions at significantly lower energies compared to those observed in the tris(amido) compounds, In[N(SiMe(3))(2)](3) (3) and In[N((t)Bu)(SiMe(3))](3) (4). The absorptions of the indium and gallium compounds were attributed to ligand-metal charge transfer transitions. Trends in the electronic transitions for compounds 2 and 3 calculated at the time-dependent density functional and configuration interaction including single excitations levels, both using a minimal basis set, were consistent with the experimental data, and Mulliken charge analyses support the assignment to ligand-to-metal charge transfer transitions. These calculations also demonstrated the presence of pi-bonding between the In and N p-orbitals, and an analogy is drawn to the frontier molecular orbitals of trimethylenemethane. The low-lying spectroscopic transition in 2, and thus its yellow color, results from mixing of the lone pair electrons on the beta-nitrogens of the hydrazido ligands with the HOMO of the InN(3) core.

Journal Article↗

Atom-efficient metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles.

The novel metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles is described. Triorganoindium compounds (R(3)In) containing alkyl, vinyl, aryl, and alkynyl groups are efficiently prepared from the corresponding lithium or magnesium organometallics by reaction with indium trichloride. The cross-coupling reaction of R(3)In with aryl halides and pseudohalides (iodide 2, bromide 5, and triflate 4), vinyl triflates, benzyl bromides, and acid chlorides proceeds under palladium catalysis in excellent yields and with high chemoselectivity. Indium organometallics also react with aryl chlorides as under nickel catalysis. In the cross-coupling reaction the triorganoindium compounds transfer, in a clear example of atom economy, all three of the organic groups attached to the metal, as shown by the necessity of using only 34 mol % of indium. The feasibility of using R(3)In in reactions with different electrophiles, along with the high yields and chemoselectivities obtained, reveals indium organometallics to be useful alternatives to other organometallics in cross-coupling reactions.

Journal Article↗

An indium:calcium phosphate colloid that specifically targets fibrin.

The ability of indium to target fibrin in vitro was evaluated. The radionuclide (114m)Indium (114mIn) was prepared as a soluble and colloidal (In:In) form, as well as, a mixed indium:calcium phosphate (In:CaP) colloid. Soluble 114mIn was prepared by maintaining acid pH (50 mM HCl). Colloidal 114mIn (In:In) was prepared under slightly basic conditions (50 mM Tris-Cl, pH 7.6). The mixed In:CaP colloid was prepared by incubation of 114mIn with calcium (10 mM) and phosphate (250 microM) under slightly basic conditions (50 mM Tris-Cl, pH 7.6). To assess fibrin binding, the three 114mIn preparations were mixed with diluted human plasma (source of fibrinogen). Fibrin polymerization was initiated by addition of calcium (5 mM) and thrombin (0.5 U/ml). Following incubation (15 min, 37 degrees C), the fibrin matrix was condensed, removed from the reaction mixture, and washed briefly. Fibrin uptake of 114mIn (soluble, colloidal, or In:CaP) was determined by gamma counting. Results demonstrated that soluble 114mIn exclusively bound a plasma protein electrophoretically and immunologically identified as transferrin. Although both colloidal 114mIn and 114mIn:CaP bound fibrin, the mixed 114mIn:CaP colloid demonstrated substantially higher fibrin binding activity (about 2-fold). The target of indium binding was confirmed as fibrin due to the presence of characteristic cross-linked gamma-gamma dimers (100 kDa) and beta-monomers (58 kDa) by SDS-PAGE. 114mIn colloid and the mixed 114mIn:CaP colloid demonstrated no ability to bind fibrin's precursor, fibrinogen. 114mIn:CaP fibrin binding was associated with formation of CaP, as evidenced by its dependence on phosphate concentration. The biocompatibility of CaP including its ability to bind 114mIn and specifically target fibrin may be of potential value for diagnostic imaging studies to identify regions of occult vascular stenosis (i.e., atherosclerotic plaques, deep vein thrombosis, pulmonary embolus).

Biocompatible Materials↗

Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3.

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

Adenocarcinoma↗