Nuclear medicine and the failed joint replacement: Past, present, and future

Soon after the introduction of the modern prosthetic joint, it was recognized that radionuclide imaging provides useful information about these devices. The bone scan was used extensively to identify causes of prosthetic joint failure. It became apparent, however, that although sensitive, regardless of how the images were analyzed or how it was performed, the test was not specific and could not distinguish among the causes of prosthetic failure. Advances in anatomic imaging, notably cross sectional modalities, have facilitated the diagnosis of many, if not most, causes of prosthetic failure, with the important exception of infection. This has led to a shift in the diagnostic paradigm, in which nuclear medicine investigations increasingly have focused on diagnosing infection. The recognition that bone scintigraphy could not reliably diagnose infection led to the development of combined studies, first bone/gallium and subsequently leukocyte/bone and leukocyte/marrow imaging. Labeled leukocyte imaging, combined with bone marrow imaging is the most accurate (about 90%) imaging test for diagnosing joint arthroplasty infection. Its value not withstanding, there are significant disadvantages to this test. In-vivo techniques for labeling leukocytes, using antigranulocyte antibodies have been explored, but have their own limitations and the results have been inconsistent. Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) has been extensively investigated for more than a decade but its role in diagnosing the infected prosthesis has yet to be established. Antimicrobial peptides bind to bacterial cell membranes and are infection specific. Data suggest that these agents may be useful for diagnosing prosthetic joint infection, but large scale studies have yet to be undertaken. Although for many years nuclear medicine has focused on diagnosing prosthetic joint infection, the advent of hybrid imaging with single-photon emission computed tomography(SPECT)/electronic computer X-ray tomography technique (CT) and the availability of fluorine-18 fluoride PET suggests that the diagnostic paradigm may be shifting again. By providing the anatomic information lacking in conventional radionuclide studies, there is renewed interest in bone scintigraphy, performed as a SPECT/CT procedure, for detecting joint instability, mechanical loosening and component malpositioning. Fluoride-PET may provide new insights into periprosthetic bone metabolism. The objective of this manuscript is to provide a comprehensive review of the evolution of nuclear medicine imaging of joint replacements

Effect of reconstruction algorithms on the accuracy of (99m)Tc sestamibi SPECT/CT parathyroid imaging

The superiority of SPECT/CT over SPECT for (99m)Tc-sestamibi parathyroid imaging often is assumed to be due to improved lesion localization provided by the anatomic component (computed tomography) of the examination. It also is possible that this superiority may be related to the algorithms used for SPECT data reconstruction. The objective of this investigation was to determine the effect of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid imaging. We retrospectively analyzed preoperative MIBI SPECT/CT parathyroid imaging studies performed on 106 patients. SPECT data were reconstructed by filtered back projection (FBP) and by iterative reconstruction with corrections for collimator resolution recovery and attenuation (IRC). Two experienced readers independently graded lesion detection certainty on a 5-point scale without knowledge of each other\u27s readings, reconstruction methods, other test results or final diagnoses. All patients had surgical confirmation of the final diagnosis, including disease limited to the neck, and location and weight of excised lesion(s). There were 135 parathyroid lesions among the 106 patients. For FBP SPECT/CT and IRC SPECT/CT sensitivity was 76% and 90% (p = 0.003), specificity was 87% and 87% (p = 0.90), and accuracy was 83% and 88% (p = 0.04), respectively. Inter-rater agreement was significantly higher for IRC than for FBP (kappa = 0.76, good agreement , versus kappa = 0.58, moderate agreement , p \u3c 0.0001). We conclude that the improved accuracy of MIBI SPECT/CT compared to MIBI SPECT for preoperative parathyroid lesion localization is due in part to the use of IRC for SPECT data reconstruction

Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of (64)Copper-asialofetuin complex in LEC rat model of Wilson\u27s disease

Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson\u27s disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson\u27s disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, (64)Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than (64)Cu. In LEC rats, (64)Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither (64)Cu-asialofetuin nor (64)Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after (64)Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that (64)Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson\u27s disease

Neutrophil Trafficking in Pulmonary Inflammation: Monitoring Migration and Blockade with 111In-Labeled Leukocytes

AbstractAim: Although imaging of In vitro labeled leukocytes is commonly used for diagnosing inflammation and infection, data concerning the use of this technique to monitor neutrophil trafficking are scarce. Here we investigated thepotential of 111In-in vitro labeled leukocytes (InWBC) to monitor neutrophil trafficking in an animal model of pulmonary inflammation.Methods: F344 rats were divided into 3 groups: Controls (received only InWBC), Inflammation (intra-tracheally challenged with lipoteichoic acid (LTA)+peptidoglycan (PGN) two hours before InWBC injection), and Blockade(pulmonary challenge with receptor blockade [LTAPGN+Antileukinate, a CXC receptor 1 and 2 antagonist]). Leukocytes were obtained from donor rats and labeled with 111In-oxine using standard procedures. Labeling efficiencyand leukocyte integrity were determined. Animals were administered 3.7-4.6 MBq InWBC via the tail vein, and were imaged 18-30 hours later and then euthanized. Post mortem the lungs were lavaged and total and differential alveolar cell counts performed. Lung tissue myeloperoxidase (MPO) activity was determined. Lung, heart, liver, spleen, kidney, marrow, intestine, blood, and muscle were harvested and organ activity/gm tissue determined. Results: InWBC labeling efficiency and cell integrity were not significantly different among groups. InWBC pulmonary activity was significantly higher (p<0.0001) in the Inflammation group (17.10 ± 2.04%) than in the Controls (1.76 ± 0.60%) and the Blockade group (9.74 ± 1.14%). Hemocytometer assessment of the bronchoalveolar lavage fluid revealed that the total number of neutrophils was significantly higher in the Inflammation group than in Controls and the Blockade group. Pulmonary MPO activity (pg/mg tissue) was significantly higher (p<0.01) in the Inflammation group (14.11 ± 5.56%) than in Controls (5.22 ± 4.77%) and the Blockade group (3.66 ± 3.77%). InWBC splenic activity was significantly higher (p<0.0001) in the Controls than in the Inflammation and Blockade groups. In the remaining organs, InWBC activity was significantly higher in the Blockade group than in the Control and the Inflammation groups.Conclusions: In a rat model of pulmonary inflammation using Antileukinate to block neutrophil chemokine receptors, InWBC accurately characterized both pulmonary and extrapulmonary neutrophil trafficking. These data indicate that InWBC may be useful to monitor both pulmonary and extrapulmonary neutrophil trafficking associated with lung inflammation and its regulation

Identificación de nuevos inhibidores del transportador de poliaminas de Trypanosoma cruzi (TcPAT11), mediante tamizado virtual

El objetivo de este trabajo es mejorar –en términos de accesibilidad y eficacia- la farmacoterapia disponible para el tratamiento de la enfermedad de Chagas. Se propone para tal fin el descubrimiento de nuevos antichagásicos guiado por el diseño racional, basado en la búsqueda de inhibidores del transportador de poliaminas de Trypanosoma cruzi (TcPAT11), mediante tamizado virtual. Inicialmente se realizó un tamizado virtual de bases de datos Drugbank y Zinc utilizando filtros de similitud molecular. La métrica empleada para la cuantificación de la similaridad fueron las huellas dactilares (fingerprints FP2) y coeficientes de Tanimoto, los cuales se calcularon por el software Openbabel.Facultad de Ciencias Exacta

Identificación de nuevos inhibidores del transportador de poliaminas de Trypanosoma cruzi (TcPAT11), mediante tamizado virtual

El objetivo de este trabajo es mejorar –en términos de accesibilidad y eficacia- la farmacoterapia disponible para el tratamiento de la enfermedad de Chagas. Se propone para tal fin el descubrimiento de nuevos antichagásicos guiado por el diseño racional, basado en la búsqueda de inhibidores del transportador de poliaminas de Trypanosoma cruzi (TcPAT11), mediante tamizado virtual. Inicialmente se realizó un tamizado virtual de bases de datos Drugbank y Zinc utilizando filtros de similitud molecular. La métrica empleada para la cuantificación de la similaridad fueron las huellas dactilares (fingerprints FP2) y coeficientes de Tanimoto, los cuales se calcularon por el software Openbabel.Facultad de Ciencias Exacta

Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells

Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c+,CD123- myeloid DC (MDC)) or immunosuppressive T cell development (CD11c-,CD123+ plasmacytoid DC (PDC)). The present study was undertaken to characterize the effects of pancreatic carcinoma cell-derived cytokines on immature monocyte-derived DC (iMo-DC) in vitro and in vivo. Medium conditioned by human pancreatic carcinoma cells inhibited iMo-DC proliferation, expression of costimulatory molecules (CD80 and CD40) and of HLA-DR, and functional activity as assessed by MLR and IL-12p70 production. iMo-DC generated from pancreatic carcinoma patients in advanced stages of the disease similarly showed decreased levels of HLA-DR expression and reduced ability to stimulate MLR in response to CD40L and IFN-gamma. Moreover, in tumor-patient peripheral blood, the ratio of MDC to PDC cells was lower than in healthy controls due to reduced numbers of MDC CD11c+ cells. Importantly, rather than a single cytokine, a combination of tumor-derived cytokines was responsible for these effects; these were primarily TGF-beta, IL-10, and IL-6, but not vascular endothelial growth factor. In summary, we have identified an array of pancreatic carcinoma-derived cytokines that cooperatively affect iMo-DC activation in a manner consistent with ineffective antitumor immune responses

FDG-PET/CT in infections: the imaging method of choice?

[No abstract available