Review of current status of targeted alpha therapy in cancer treatment.

Targeted alpha therapy is an emerging alternative for palliative therapy of a wide range of tumor types. Data from preclinicaland clinical research demonstrates a high potential for the selective killing of tumor cells and minimal toxicity to surroundinghealthy tissues. This article summarizes the developmental stages of alpha-targeted therapy from benchtop to commercialization.It discusses fundamental properties, production pathways, microdosimetry, and possible targeting vectors. Proper coverage hasalso been given to comparing it with other standard treatment procedures while exploring clinical applications of alpha emitters.In the end, like other therapies, the challenges it faces and its future impact on personalized medicine are also illustrated.

Radiosynthesis, quality control, biodistribution, and infection-imaging study of a new 99mTc-labeled ertapenem radiopharmaceutical.

Ertapenem is a member of carbapenem antibiotics used for the treatment of moderate-to-severe intra-abdominal, urinary tract, acute pelvic, and post-surgical gynecologic infections. The antibacterial activity of ertapenem is mediated through binding to penicillin-binding proteins which results in inhibiting the cross-linking of the peptidoglycan layer of the bacterial cell wall. Therefore, ertapenem can be labeled with technetium-99m (99mTc), a gamma emitter radionuclide, for the diagnosis of deep-seated bacterial infections, such as urinary tract, intra-abdominal, osteomyelitis, and post-surgical gynecologic infections. The labeling procedure was carried out by varying the reaction conditions, such as the amount of the ligand and reducing agent, pH, reaction time and temperature, and radioactivity. At optimized reaction conditions more than 93% 99mTc-ertapenem radioconjugate was obtained. 99mTc-ertapenem was found 90% intact in saline medium up to 6 h, while 88% intact in human blood serum up to 3 h. Biodistribution study showed target-to-non-target ratios of 2.91 ± 0.19, 2.39 ± 0.31, and 1.23 ± 0.22 in S. aureus, E. coli, and turpentine oil-infected rat models, respectively. The SPECT scintigraphy showed high uptake of 99mTc-ertapenem in bacterial-infected abscesses, and low counts were recorded in normal and turpentine oil-inflamed tissues. In conclusion, 99mTc-ertapenem can be a potent infection-imaging agent, which can diagnosis deep-seated bacterial infections at early stage but need further pre-clinical evaluation in variety of infection models.

Facile One-Pot Strategy for Radiosynthesis of 99mTc-Doxycycline to Diagnose Staphylococcus aureus in Infectious Animal Models.

The accurate and early diagnosis of infection is an important feature in the biomedical sciences for better treatment and to decrease the rate of morbidity associated with diseases. Doxycycline (DC) is a semisynthetic antibiotic that belongs to tetracycline family and usually prescribed to treat a variety of infections. The objective of the present research work was to develop a new radiopharmaceutical 99mTc-Doxycycline (99mTc-DC), by using SnCl2·2H2O as a reducing agent for diagnostic applications. It was confirmed through this study that 99mTc-DC possessed high radiolabeling yield (95%). In vitro studies were performed by incubating 99mTc-DC in human serum at 37 °C. The in vitro binding interaction of the labeled antibiotic was analyzed with bacterial strain (live Staphylococcus aureus cells), and its stability was further determined. Moreover, for in vivo infection imaging study, the infection was induced with S. aureus (gram positive) cells intramuscularly injected in mice models followed by biodistribution studies for 99mTc-DC that were performed. Biodistribution studies of 99mTc-DC showed that the radiotracer was significantly accumulated at the site of infection and indicated the renal route of excretion. Scintigraphic images obtained as a result of in vivo study showed good uptake of prepared radiotracer (99mTc-DC) in the infectious lesions at 1-, 4-, and 24-h post-injection. Target-to-non-target ratios for 99mTc-DC were significantly different for the infectious lesions and non-infected tissues and remained 2.13 ± 0.3 up to 24-h post-injection of 99mTc-DC. 99mTc-DC showed preferential binding to living bacterial infected sites as compared to other parts of the body, and thus it can be inferred that 99mTc-DC might be a potential candidate to diagnose the infection.

Radiolabeling, quality control, and biological characterization of 177 Lu-labeled kanamycin.

Kanamycin is an antibiotic, isolated from Streptomyces kanamyceticus, which is used to treat serious bacterial infections. The fact that the present radioligand 99m Tc-kanamycin used for diagnosis is short-lived, raised a need to label and study kanamycin with one of the most important beta (ß) radiation emitting isotope 177 Lu. Labeling yield of 177 Lu-kanamycin was confirmed by different chromatography techniques such as paper chromatography, TLC, HPLC. Several experiments were performed to optimize labeling with changing reaction conditions such as pH, temperature, amount of ligand, and reaction time. In vitro stability analysis was performed incubation with human serum. Electrophoresis analysis was also conducted to determine the charge on 177 Lu-kanamycin. The biodistribution and scintigraphy were performed in normal mice and rabbit, respectively, at different time intervals of postinjection. 177 Lu-kanamycin was prepared with very high yield (~100%), with excellent stability in vivo and in vitro (>99% 6 hr postprep.), at pH 7. Maximum labeling was achieved at less reaction time (15 min), with maximum conjugation of the ligand (12.5 mg) with 177 Lu. Electrophoresis analysis showed net neutral charge. The radioligand showed rapid clearance from body in biodistribution and scintigraphy studies. The preparation 177 Lu-kanamycin could be used as a radio-pharmaceutical for infection imaging purpose, especially when transporting the radioligand to long-range distances.

Corrigendum to "Extraction of HCV-RNA from Plasma Samples: Development towards Semiautomation".

[This corrects the article DOI: 10.1155/2015/367801.].

Extraction of HCV-RNA from Plasma Samples: Development towards Semiautomation.

A semiautomated extraction protocol of HCV-RNA using Favorgen RNA extraction kit has been developed. The kit provided protocol was modified by replacing manual spin steps with vacuum filtration. The assay performance was evaluated by real-time qPCR based on Taqman technology. Assay linearity was confirmed with the serial dilutions of RTA (Turkey) containing 1 × (10(6), 10(5), 10(4), and 10(3)) IU mL(-1). Comparison of test results obtained by two extraction methods showed a good correlation (r = 0.95, n = 30) with detection limit of 10(2) IU mL(-1). The semiautomated vacuum filtration based protocol demonstrated high throughput: 35 minutes for the extraction of a batch of 30 samples (150 µL each) with reduced labor, time, waste, and cost. Performance characteristics of semiautomated system make it suitable for use in diagnostic purpose and viral load determinations.

A review on 129I analysis in air.

A review of literature focused on (129)I determination in air is provided. (129)I analysis in the environment represents a vital tool for tracing transport mechanisms, distribution pathways, safety assessment and its application as environmental tracer. To achieve that, specific chemical extraction methods and high sensitivity analytical techniques have been developed. This paper is intended to give an overview about the sample collection, extraction and distribution of (129)I in the air. Sensitivity of available measurement techniques for the determination of (129)I is compared. The article also provides the summary of current worldwide distribution of (129)I in air and respective radiation exposure of man.

Investigation of the isotopic ratio 129I/I in petrified wood.

In fossil specimens, measurements of the natural isotopic ratio (129)I/I may provide a method to estimate the age of sample. The motivation for measuring the isotopic composition ((129)I/I) of petrified wood samples collected from Austria was to check this feasibility. Alkaline fusion together with anion exchange was used to extract iodine from the sample. Typical sample size for this study was 10-90 g. An atomic ratio as low as 10(-14) was determined using accelerator mass spectrometry (AMS). Uranium concentrations measured by instrumental neutron activation analysis (INAA) and α-spectrometry were found to be less than 3 mg kg(-1), therefore the contribution from fissiogenic (129)I was small and an estimation of ages was based on the decrease of the initial ratio (due to decay of the cosmogenic (129)I in a closed system) after subtraction of the fissiogenic (129)I. The value of the prenuclear ratio is crucial for the use of the (129)I system for dating purposes in the terrestrial environment. From the preanthropogenic (initial) ratio of 1.5 × 10(-12) of the hydrosphere and the results of the present study for the samples from Altenburg (1.05 × 10(-12)) and Fuerwald (6.16 × 10(-13)), respective ages of 8 ± 2.2 and 20.2 ± 2.2 million years were derived. Since samples were collected from a stratum deposited in the Upper Oligocene/Ergerien period (~25-30 million years ago), it can be concluded that these isotopic ratios do not show ages but an elapsed time since fossil wood was isolated from mineral rich water. Paleontological investigation shows that samples from Altenburg had mixed characteristics of old and modern Tertiary plants, thus an origin from a younger stratum re-sedimented with Oligocene cannot be excluded. However, the sample from Drasenhofen reflects that the (129)I/I system might not always be suitable for the dating of petrified wood sample due to fixation of anthropogenic (129)I into surface fractures.

Iodine isotopes (127I and 129I) in aerosols at high altitude Alp stations.

Concentrations of gases and particulate matter have been proven to be affected by meteorological and geographical variables from urban locations to high mountain clean air sites. Following our previous research in Vienna, we summarize here new findings about concentration levels of iodine isotopes in aerosols collected at two Alpine meteorological stations, Sonnblick (Austria) and Zugspitze (Germany) during 2001. The present study mainly focuses on the effect of altitude on the anthropogenic concentration of (129)I and on the isotopic ratio (129)I/(127)I. Iodine was separated from matrix elements by using either an anion exchange method or solvent extraction, and was analyzed by ICP-MS and AMS. Over the altitude change from Vienna to Zugspitze and Sonnblick (202 m to 2962 m and 3106 m above sea level), stable iodine level decreased from an average of 0.94 ng m(-3) to 0.52 ng m(-3) and 0.62 ng m(-3), respectively. Similarly, (129)I concentrations at both Alpine stations were about 1 order of magnitude lower (10(4) atoms m(-3)) than values obtained for Vienna (10(5) atoms m(-3)) and reveal a strong vertical concentration gradient of (129)I. A high degree of variability is observed, which is due to wide variation in the origin of air masses. Furthermore, air trajectory analysis demonstrates the importance of large scale air transport mostly from southeast Europe for influencing Sonnblick whereas influence from northwest Europe is strong at Zugspitze. In contrast to (129)I, a higher concentration of (7)Be was found at higher altitude stations compared to Vienna which probably results from its production in the upper atmosphere.

Retrospective measurements of airborne 129iodine in Austria.

The knowledge about the distribution of anthropogenic (129)I is crucial for a successful establishment of transport mechanisms, fate and behaviour in the environment. In present study, the historical record of dry deposition of (129)I in Austria over four decades back to the 1960s is reconstructed. The (129)I/(127)I isotopic ratio of the order of 10(-9)-10(-7) in airborne particles revealed a prominent anthropogenic (129)I signature. The time profile of airborne (129)I follows directly the pattern of the gaseous emissions from European reprocessing plants. Furthermore, temporal variations of (129)I were traced monthly over two years. The potential risks of internal exposure to (129)I are associated with both inhalation and ingestion. Since dose via inhalation was found insignificant, the thyroid equivalent dose from the internal exposure of (129)I using a value of 10(-8) for the isotopic ratio (129)I/(127)I in the thyroid and ICRP reference man was calculated. The corresponding thyroid cancer risk factor of 10(-11) for an adult from life-time exposure is one order of magnitude higher than for a 1-year old child. Due to low radiation toxicity of (129)I the annual dose is 8 × 10(4) times lower than the dose limit of the National Research Council, USA which is 0.04 mSv y(-1) to whole body or any organ for a combined beta and photon emitting radionuclide.