Comparative radionuclide and thermodilution determinations of cardiac output and stroke volume in the baboon (Papio ursinus)

Thermodilution cardiac output determinations and multigated equilibrium blood-pool scintigraphy were performed in ten healthy chacma baboons (Papio ursinus). The correlation was moderately good between both the radionuclide and thermodilution stroke volume (r = 0.58, SEE = 3 ml; SVth = 0.78SVr + 15.6 ml) as well as the cardiac output (r = 0.72, SEE = 0.2 liter/min; COth = 0.56 Cor + 2.1 liter/min). The attenuation depth dr as determined by radionuclide techniques was found to correlate well with the radiologically determined values dx (r = 0.8, SEE = 0.4 cm; dx = 0.87dr + 0.72 cm) which validated the depth values used in the calculations.     

Will imaging of apoptosis play a role in clinical care? A tale of mice and men

Programmed cell death (apoptosis) plays a role in the pathophysiology of many diseases and in the outcome of treatment. Apoptosis is the likely mechanism behind the cytoreductive effects of standard chemotherapeutic and radiation treatments, rejection of organ transplants, cellular damage in collagen vascular disorders, and delayed cell death due to hypoxic-ischemic injury in myocardial infarction and neonatal hypoxic ischemic injury. Observations about the role of apoptosis have fueled the development of novel agents and treatment strategies specifically aimed at inducing or inhibiting apoptosis.Despite these research developments there are no clinical entities where specific measures of apoptosis are used in either diagnosis or patient management. Part of the difficulty in bridging the gap between the basic science understanding of apoptosis and the clinical application of this information is the lack of a sensitive marker to monitor programmed cell death in association with disease progression or regression. Technetium-99m labeled annexin V localizes at sites of apoptosis in-vivo, due to its nanomolar affinity for membrane bound phosphatidylserine. Radiolabeled annexin V imaging permits identification of the site and extent of apoptosis in experimental animals. Annexin V has been successfully used in animal models to image organ transplant rejection, characterize successful therapy of tumors, pinpoint acute myocardial infarction, and identify hypoxic ischemic brain injury of the newborn and adult. Early studies in human subjects suggest that ^99mTc annexin imaging will be also be useful to identify rejection in transplant recipients, localize acute myocardial infarction, and characterize the effectiveness of a single treatment in patients with tumors.This review describes the imaging approaches to detect and monitor apoptosis in-vivo that are presently in early clinical trials. The preliminary data are extrapolated to identify conditions where apoptosis imaging may be valuable in clinical decision making. These conditions include: transplant rejection; hypoxic/ischemic injury of heart and brain; and determining the efficacy of therapy in cancer, heart failure and osteoporosis.     

Speciation and Bioavailability Measurements of Environmental Plutonium Using Diffusion in Thin Films

The biological uptake of plutonium (Pu) in aquatic ecosystems is of particular concern since it is an alpha-particle emitter with long half-life which can potentially contribute to the exposure of biota and humans. The diffusive gradients in thin films technique is introduced here for in-situ measurements of Pu bioavailability and speciation. A diffusion cell constructed for laboratory experiments with Pu and the newly developed protocol make it possible to simulate the environmental behavior of Pu in model solutions of various chemical compositions. Adjustment of the oxidation states to Pu(IV) and Pu(V) described in this protocol is essential in order to investigate the complex redox chemistry of plutonium in the environment. The calibration of this technique and the results obtained in the laboratory experiments enable to develop a specific DGT device for in-situ Pu measurements in freshwaters. Accelerator-based mass-spectrometry measurements of Pu accumulated by DGTs in a karst spring allowed determining the bioavailability of Pu in a mineral freshwater environment. Application of this protocol for Pu measurements using DGT devices has a large potential to improve our understanding of the speciation and the biological transfer of Pu in aquatic ecosystems.     

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Single and double isotope labeling of social insect colonies: Gamma-emitting radionuclides as individually identifiable markers

Gamma-emitting radionuclides were used in single and double-isotope combinations to label individual colonies of the subterranean termite Reticulitermes flavipes Kol. Each of these radionuclides produces a characteristic and identifiable energy spectrum upon decay, and using whole-body gamma spectroscopy, the characteristic spectral emission signatures of each isotope and their relative quantities were detected in workers, brachypterous nymphs, and alates.Radionuclides present in a food source were rapidly incorporated into workers, and reached detection limits within one to three days. Isotopic labels were transferable between colony members, and all individuals in laboratory colonies were labeled within 21 days of initial contact with foragers that had fed at a labeled food source.Single- and double-label nuclide markers were transferred to sexual forms (prealates and alates) by social food flow. Applications of radionuclide labeling and gamma spectroscopic analysis in insect behavioral ecology are discussed.

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Résumé Des radionucléides ont été utilisés seuls ou en combinaison par 2 pour marquer des individus de colonies de Reticulitermes flavipes. Chaque radionucléide possède ses caractères spectraux. Avec un spectroscope très sensible, pouvant contenir l'insecte entier, il est possible d'identifier les signatures spectrales de chaque isotope et les quantités relatives de chacun d'eux chez les ouvriers, les larves brachyptères et les ailés.Les radionucléides présents dans le papier consommé sont rapidement incorporés chez les ouvriers, et atteignent le seuil de détection en 1 à 3 jours. Le marquage isotopique se transmet entre les membres de la colonie; tous les habitants de colonies de laboratorie ont été contaminés en 21 jours, après des contacts avec des individus alimentés sur une source marquée.Les marqueurs isotopiques avec 1 ou 2 radionucléides sont transférés aux sexués par les échanges trophallaxiques. La discussion porte sur les applications du marquage aux radionucléides et l'analyse au spectroscope en écologie éthologique des insectes.

     

Measuring contaminant transport rates between water and sediments using limnocorrals

Radiotracers injected as soluble salts into 1.2 m³ limnocorrals in a shallow dystrophic lake were transported rapidly (2 to 12% d^–1) from the water to the bottom sediments. Removal rates of most contaminants declined after 14 days. Tracers were removed from the water much more rapidly than stable element analogs present naturally. After 3 weeks Am, Co, Ra, Hg, Sn and Fe activities on the enclosure walls were greater than 15% of the activity in the water. However, activity on the walls was a small fraction (< 6%) of the total amount of tracer injected. Particle fluxes inside the corrals were lower and much less variable than those measured outside. This difference appears to result from greater resuspension of bottom sediments in the lake than in the enclosures. Both particle-bound and soluble tracers were measured in cores of bottom sediments. Tracer sorption onto particles, diffusion into the bottom sediments, and uptake on the plastic enclosure walls were rapid and reversible. Tracer kinetics were very reproducible in replicate enclosures, providing a simple, experimental system in which limnological conditions can be manipulated. Loss rates and distributions of stable isotopes and radioisotopes can be used to develop and test a general model of element transport applicable to both short and long term analyses.     

Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution

Targeted internal radionuclide therapy (TRT) could be an efficient, specific way to treat disseminated melanoma. Based on a previous pharmacomodulation study, we selected a quinoxaline-derived molecule (ICF01012) for its melanin specificity and kinetic properties suitable for TRT. Here, we determined the efficacy of [¹³¹I]ICF01012 radiotherapy in vitro and in vivo in relation to melanogenesis using human melanoma models. [¹²⁵I]ICF01012 uptake was first assessed in relation to melanin content. We found that melanin distribution in different models was representative of pathology seen in human tumours: melanin content was high in the extracellular space of SKMel3 tumours, and accumulated primarily in melanophages in M4Beu tumours. Targeted [¹³¹I]ICF01012 radiotherapy had a strong anti-tumoural efficacy in pigmented versus unpigmented tumours, regardless of target distribution and content. This study supports the use of melanin targeting with ¹³¹I-labelled iodoquinoxaline for effective treatment of melanoma.     

Reducing the renal retention of low- to moderate-molecular-weight radiopharmaceuticals

The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with minimal background. Unfortunately, they are often reabsorbed in the kidneys, leading to possible nephrotoxicity, limiting the therapeutic dose, and/or reducing imaging quality. The blocking of endocytic receptors has been extensively used as a strategy to reduce kidney radiation. Alternatively, the physicochemical properties of radiotracers can be modulated to either prevent their reuptake or promote the excretion of radiometabolites. Other interesting strategies focus on the insertion of a cleavable linker between the radiolabel and the targeting moiety or pretargeting approaches in which the targeting moiety and radiolabel are administered separately. In the context of this review, we will discuss the latest advances and insights on strategies used to reduce renal retention of low- to moderate-molecular-weight radiopharmaceuticals.     

Cardiac assessment of patients with late stage Duchenne muscular dystrophy

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients. Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA. Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA. Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232–7.)