Toward maintaining canine training aid integrity: Visualizing contamination and testing storage materials for a non-hazardous canine training aid.

Contamination of canine training aids is a pervasive issue that may lead to incorrect canine discrimination of target odors. It is therefore important to properly store training materials to maintain their integrity and efficiency. First, this study demonstrated the potential for contamination using GloGerm™ as a proxy for odor/particulate transfer. Then, eight types of containers were evaluated to determine (1) the ability to prevent odor permeation and (2) the likelihood of maintaining the ab/adsorbed odor. Lastly, a longitudinal study evaluated how the permeation of the target odor changed over time. Analysis occurred using a direct analysis in real-time mass spectrometer (DART-MS) to detect triacetone triperoxide (TATP) from the non-hazardous canine training aid known as the polymer odor capture-and-release (POCR) system. Results showed that Mylar and Opsak bags were most effective for short-term storage, maintaining low levels of ab/adsorption. Over time, the amount of TATP permeating through the primary containers and collecting in a secondary container (i.e., outer packaging) increased at 1 week and decreased thereafter (up to 4 months). The amount of TATP collecting in the primary containers, however, increased up to 1 month and decreased thereafter.

An Overview of Treatment Approaches for Octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX) Explosive in Soil, Groundwater, and Wastewater.

Octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX) is extensively exploited in the manufacturing of explosives; therefore, a significant level of HMX contamination can be encountered near explosive production plants. For instance, up to 12 ppm HMX concentrations have been observed in the wastewater effluent of a munitions manufacturing facility, while up to 45,000 mg/kg of HMX has been found in a soil sample taken from a location close to a high-explosive production site. Owing to their immense demand for a variety of applications, the large-scale production of explosives has culminated in severe environmental issues. Soil and water contaminated with HMX can pose a detrimental impact on flora and fauna and hence, remediation of HMX is paramount. There is a rising demand to establish a sustainable technology for HMX abatement. Physiochemical and bioremediation approaches have been employed to treat HMX in the soil, groundwater, and wastewater. It has been revealed that treatment methods such as photo-peroxidation and photo-Fenton oxidation can eliminate approximately 98% of HMX from wastewater. Fenton's reagents were found to be very effective at mineralizing HMX. In the photocatalytic degradation of HMX, approximately 59% TOC removal was achieved by using a TiO2 photocatalyst, and a dextrose co-substrate was used in a bioremediation approach to accomplish 98.5% HMX degradation under anaerobic conditions. However, each technology has some pros and cons which need to be taken into consideration when choosing an HMX remediation approach. In this review, various physiochemical and bioremediation approaches are considered and the mechanism of HMX degradation is discussed. Further, the advantages and disadvantages of the technologies are also discussed along with the challenges of HMX treatment technologies, thus giving an overview of the HMX remediation strategies.

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in ß-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 µg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 µg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 µg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

A sketch of microbiological remediation of explosives-contaminated soil focused on state of art and the impact of technological advancement on hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation.

When high-energy explosives such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), 2,4,6-trinitrotoluene (TNT) are discharged into the surrounding soil and water during production, testing, open dumping, military, or civil activities, they leave a toxic footprint. The US Environmental Protection Agency has labeled RDX as a potential human carcinogen that must be degraded from contaminated sites quickly. Bioremediation of RDX is an exciting prospect that has received much attention in recent years. However, a lack of understanding of RDX biodegradation and the limitations of current approaches have hampered the widespread use of biodegradation-based strategies for RDX remediation at contamination sites. Consequently, new bioremediation technologies are required to enhance performance. In this review, we explore the requirements for in-silico analysis for producing biological models of microbial remediation of RDX in soil. On the other hand, potential gene editing methods for getting the host with target gene sequences responsible for the breakdown of RDX are also reported. Microbial formulations and biosensors for detection and bioremediation are also briefly described. The biodegradation of RDX offers an alternative remediation method that is both cost-effective and ecologically acceptable. It has the potential to be used in conjunction with other cutting-edge technologies to further increase the efficiency of RDX degradation.

In situ identification of TATP and DADP particles collected with transparent tape by Raman spectroscopy and imaging.

Triacetone triperoxide (TATP) and its byproduct diacetone diperoxide (DADP) are commonly used home-made high explosives in bombing cases and terrorist attacks. However, these two peroxide explosives are unstable and prone to thermal decomposition, leading to challenges in sample collection and preparation in bombing cases. Therefore, there is an urgent need to develop an in situ identification method for TATP and DADP. Compared to the solvent-based swabbing methods commonly used for trace explosive collection, the tape lifting method can collect explosive particles and other potential evidence without damaging fingerprints or DNA. This study aims to develop a tape lifting method to collect trace explosive particles in bombing cases and an in situ method to identify TATP and DADP particles on the sticky side of transparent tape directly using laser confocal Raman spectroscopy. One type of fingerprint tape and two types of office tape were used to collect peroxide explosive particles followed by particle fixation on glass slides. Laser confocal Raman spectroscopy was applied to directly identify target particles, without peeling the attached tape off the glass slide. A solid-state laser emitting at 473 nm was suitable for Raman and imaging analysis of TATP and DADP. To mimic the real situation, the synthetic TATP and DADP were passed through a 100-mesh sieve, respectively. Fifty µg of each explosive powder was weighed, mixed and spread on a wooden table with dust in an area of 10 × 10 cm2. Subsequently, the samples were collected with the fingerprint tape. A targeted area of the tape with suspicious particles was imaged for analysis. Based on the difference between the characteristic Raman bands of TATP and DADP, the band ranges of 530-550 cm-1 and 750-770 cm-1 were selected, respectively, for obtaining the distribution information. The combination of Raman technology and the tape lifting method shows great potential for in situ identification of forensic samples by providing chemical and spatial information.

Bioaugmentation for remediation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) contaminated soil using a clay based bioformulation.

Bioaugmentation is an important remediation strategy for hazardous organic compounds. A microcosm study was conducted to evaluate the remediation of soils contaminated with hazardous high explosive, Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) using an eco-friendly bioformulation. Janibacter cremeus, an enriched indigenous soil bacterium isolated from the explosive contaminated site was immobilized in a mixture of calcite and cocopeat for bioaugmentation. The developed bioformulation showed a consistent viability for 150 days, at 4 °C storage conditions. HMX at field concentrations was degraded in microcosms for 35 days under unsaturated (aerobic) and saturated (anoxic) moisture conditions. Negligible degradation was observed under unsaturated moisture conditions, whereas, saturated conditions led to substantial decrease in HMX. Mass spectrometric (MS) analysis revealed the formation of nitroso derivatives of HMX during the anoxic degradation. Also, observed was the presence of 5-hydroxy-4-nitro-2,4-diazapentanal, a precursor of 4- nitro-2,4-diazabutanal, which eventually could be mineralized. An inexpensive and natural carrier when chosen for immobilization of explosive degrading microbes was found to be effective in the in situ remediation of explosive.

Paper spray ionization-high-resolution mass spectrometry (PSI-HRMS) of peroxide explosives in biological matrices.

Mitigation of the peroxide explosive threat, specifically triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD), is a priority among the law enforcement community, as scientists and canine (K9) units are constantly working to improve detection. We propose the use of paper spray ionization-high-resolution mass spectrometry (PSI-HRMS) for detection of peroxide explosives in biological matrices. Occurrence of peroxide explosives and/or their metabolites in biological samples, obtained from urine or blood tests, give scientific evidence of peroxide explosives exposure. PSI-HRMS promote analysis of samples in situ by eliminating laborious sample preparation steps. However, it increases matrix background issues, which were overcome by the formation of multiple alkali metal adducts with the peroxide explosives. Multiple ion formation increases confidence when identifying these peroxide explosives in direct sample analysis. Our previous work examined aspects of TATP metabolism. Herein, we investigate the excretion of a TATP glucuronide conjugate in the urine of bomb-sniffing dogs and demonstrate its detection using PSI from the in vivo sample.

A laboratory study on dissipation and risk assessment of the proinsecticide thiocyclam and its metabolite nereistoxin in tomato using liquid chromatography high resolution mass spectrometry.

Reduced pesticides use, alongside increased organic farming, has created a need for new biological products, such as thiocyclam, to control pests. Thiocyclam has scarcely been studied, making the study of its degradation in fruits and vegetables, such as tomatoes, an urgent requirement. To monitor thiocyclam metabolites in tomato, dissipation studies were carried out using a liquid chromatography-Orbitrap mass spectrometry (UHPLC-Orbitrap MS) method for 60-days after foliar application. Thiocyclam was not persistent (DT50 < 15 days), but nereistoxin - its primary metabolite - remained present in the tomatoes for >60 days. Four nereistoxin metabolites, detected at low concentrations (<100 µg/kg), were also monitored. This is the first time a study has provided dissipation patterns for thiocyclam and nereistoxin. The results obtained suggest revising the legislation concerning these compounds is required. Toxicological studies must also be carried out because there is no toxicity data currently for thiocyclam or nereistoxin.

Evolution and Correlation of cis-2-Methyl-4-propyl-1,3-oxathiane, Varietal Thiols, and Acetaldehyde during Fermentation of Sauvignon blanc Juice.

cis-2-Methyl-4-propyl-1,3-oxathiane (cis-2-MPO) was recently identified in wine and proposed to arise from the reaction of 3-sulfanylhexan-1-ol (3-SH) and acetaldehyde. However, the evolution profile of cis-2-MPO during alcoholic fermentation (AF) and storage and its relationship with varietal thiols and acetaldehyde production were unknown. These aspects were investigated by fermenting Sauvignon blanc juice with J7 and/or VIN13 yeast strains and assessing the stability of cis-2-MPO during wine storage. Moderate to strong Pearson correlations verified similar evolution trends between acetaldehyde, 3-sulfanylhexyl acetate, and cis-2-MPO, with initial increases and a peak during the early to middle stages of AF before consecutive decreases until the end. Contrarily, 3-SH correlated moderately only at the end of AF. A consistent decrease observed for cis-2-MPO when spiked into Sauvignon blanc wine and assessed during 1-year storage revealed its general instability, but acetaldehyde addition (100 mg/L), pH 3.0, and storage at 4 °C all appeared to retain cis-2-MPO. These results have implications for wine aroma and the potential for cis-2-MPO to act as a sink (or source) for 3-SH in wine over time.

A field-applicable colorimetric assay for notorious explosive triacetone triperoxide through nanozyme-catalyzed irreversible oxidation of 3, 3'-diaminobenzidine.

A field-applicable colorimetric assay for fast detection of notorious explosive triacetone triperoxide (TATP) has been developed through the selective irreversible oxidation of 3, 3'-diaminobenzidine by hydrogen peroxide (HP) liberated during the acidic hydrolysis/degradation of TATP in the presence of MnO2 nanozymes. The generated HP was detected by probing the absorbance of the product (indamine polymer) of the 3, 3'-diaminobenzidine (DAB) oxidation reaction at 460.0 nm. The UV-Vis measurements provided a linear range from 1.57 to 10.50 mg L-1 TATP with a detection limit of 0.34 mg L-1. The oxidation of DAB cannot proceed by molecular oxygen, thus it is selectively oxidized by H2O2; this prevents false-positive results from laundry detergents (containing O2-releasing substances). Moreover, a naked-eye field test was developed, and a fast spot test analyzing time of 5 s was achieved. The selectivity of the assay was checked by analyzing some synthetic samples prepared with a laundry detergent as camouflage. The results of the developed assay revealed quantitative recoveries for TATP whereas the standard nanozyme-based method showed significant false-positive results. Graphical abstract.

A novel hydrophilic interaction liquid chromatography method for the analysis of arterolane; Isolation and structural elucidation of its major degradation product by LC-HRMS and NMR.

Adequate retention of arterolane (ART) has not been published in the literature till date; the hydrophilic interaction liquid chromatographic (HILIC) method with improved retention and separation of arterolane from its degradation products are reporting here for the first time. The present study discusses the comparative retention of the drug-using Reverse Phase C18 and HILIC columns, indicating the effective method (Syncronis HILIC-150 x 4.6 mm, 5µ). It was observed that the buffer concentration (ammonium acetate) in the mobile phase plays a crucial role in the retention of ART. Forced degradation studies of ART were conducted as per ICH Q1 (R2) prescribed conditions. The drug is not stable in hydrolytic (acid, base and neutral), oxidative and photolytic conditions and observed four unique degradation products (DPs). The optimized method for the analysis of degraded samples comprises of Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) technique having Agilent HILIC plus (100 × 4.6 mm, 3.5µ) column and acetonitrile (ACN) and 10 mM ammonium acetate 75:25 (% v/v) mobile phase with 0.4 mL/minute flow. Initially, the structure of all four DPs was proposed on the basis of accurate mass and their fragmentation pattern. The major degradation product (DP4) was isolated, and its structure was confirmed by HRMS and 1H NMR, 13C NMR, HMBC, DEPT 135 and Deuteriated NMR spectroscopy. The formation of DPs might be due to the breakdown of (1 r,3r,5 r,7r)-2-methoxyadamantan-2-ol from ART (DP4), and subsequent diol formation at 1,2,4-trioxolane moiety (DP3).

Combined 68Ga-NOTA-Evans Blue Lymphoscintigraphy and 68Ga-NOTA-RM26 PET/CT Evaluation of Sentinel Lymph Node Metastasis in Breast Cancer Patients.

In this study, we applied a new strategy to identify sentinel lymph node (SLN) metastasis by combining 68Ga-NOTA-Evans Blue (68Ga-NEB) for SLN mapping and 68Ga-NOTA-RM26 for LN metastasis detection in breast cancer patients. A total of 24 female patients with breast cancer diagnosed by core biopsy or suspected by mammography or ultrasonography were recruited and provided informed consent. All patients underwent 68Ga-NEB and 68Ga-NOTA-RM26 PET/CT imaging. Visual analysis of 68Ga-NEB PET/CT images was used to determine SLNs, and then compared with the 68Ga-NOTA-RM26 results and histopathological findings. SLNs were visualized in 24 of 24 patients (100.0%) within 4.0-10.0 (5.6 ± 1.4) min. All patients were pathologically diagnosed with breast cancer, and 12 patients had ipsilateral lymph node metastasis. By combining 68Ga-NEB and 68Ga-NOTA-RM26 images, 7/12 (58.3%) patients showed mild to intense uptake of 68Ga-NOTA-RM26 in SLNs, 1/12 patient (8.3%) had moderate uptake of 68Ga-NOTA-RM26 in the non-SLNs rather than SLN, indicating possible bypass lymphatic drainage, partially accounting for the false negatives in SLN biopsy during surgery. No false positives were found. The SUVmax of 68Ga-NOTA-RM26 activity in metastatic SLNs was significantly higher than that in non-metastatic SLNs (2.2 ± 2.3 vs 0.7 ± 0.1, P = 0.047). This study manifests the value of combination of 68Ga-NEB and 68Ga-NOTA-RM26 dual tracer PET/CT in preoperative evaluation of SLN metastasis in breast cancer patients, especially in those patients with lymphatic obstruction and bypass drainage. In general, positive 68Ga-NOTA-RM26 uptake in either SLN or other lymph nodes can apply lymph node dissection rather than intraoperative SLN biopsy.

Solid-State Fluorescence-based Sensing of TATP via Hydrogen Peroxide Detection.

Fluorenylboronate ester chromophore-based thin films were investigated for the detection of triacetone triperoxide (TATP) vapors via the decomposition product, hydrogen peroxide. Sensing with a high level of sensitivity was achieved using a fluorescence "turn-on" mechanism based on the significant shifts in the absorption and photoluminescence spectra that occurs when the boronate esters were converted to phenoxides by hydrogen peroxide under basic conditions. The addition of an organic base was found to be critical for achieving fast conversion reactions and the formation of the phenoxide anions. Addition of a nitrile group to the fluorenyl boronate ester moiety improved the stability of the material to photooxidation, increased the photoluminescence quantum yields, and enhanced the absorption and emission shifts to longer wavelengths. In real-time sensing measurements, films comprising the cyanofluorenyl boronate ester moiety and tetra- n-butylammonium hydroxide had a response time to acid-decomposed TATP vapor of seconds and a limit of detection of 40 ppb in 60 s.

Quantitative determination of cyclic phosphatidic acid and its carba analog in mouse organs and plasma using LC-MS/MS.

Cyclic phosphatidic acid (cPA), an analog of lysophosphatidic acid, is involved in the regulation of many cellular processes. A sensitive and specific method to quantify the molecular species of cPA is important for studying the physiological and pathophysiological roles of cPA. Here, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantification method for the simultaneous detection of cPA species having various fatty acids (16:0, 18:0, 18:1, and 18:2) as well as 2-carba-cPA, a chemically synthesized analog of cPA. Chromatography was performed using a reversed-phase C18 column. cPA species were detected using a triple quadrupole mass spectrometer. cPA 17:0 was used as an internal standard. Intra- and interday precision values (CV%) were within 10%. The linear range of detection for each cPA species was 0.01 µg/mL to 5 µg/mL, with correlation coefficients of 0.998 or higher. The developed method was applied to the quantification of cPA species in mouse plasma and organs. The concentrations of cPA 16:0, 18:0, and 18:1 were revealed to be significantly reduced in the brains of cuprizone-treated mice, a model of multiple sclerosis, compared with control mice. These findings could be important for understanding the roles of cPA in the neurodegenerative processes associated with multiple sclerosis.

Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT. / Valor de las imágenes de 177Lu-PSMA post-terapia para una interpretación precisa de la respuesta a la terapia con PET/TC con 68Ga-PSMA.

A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/ml. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results.

Use of Mass Spectrometric Vapor Analysis To Improve Canine Explosive Detection Efficiency.

Canines remain the gold standard for explosives detection in many situations, and there is an ongoing desire for them to perform at the highest level. This goal requires canine training to be approached similarly to scientific sensor design. Developing a canine training regimen is made challenging by a lack of understanding of the canine's odor environment, which is dynamic and typically contains multiple odorants. Existing methodology assumes that the handler's intention is an adequate surrogate for actual knowledge of the odors cuing the canine, but canines are easily exposed to unintentional explosive odors through training material cross-contamination. A sensitive, real-time (∼1 s) vapor analysis mass spectrometer was developed to provide tools, techniques, and knowledge to better understand, train, and utilize canines. The instrument has a detection library of nine explosives and explosive-related materials consisting of 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2,4,6-trinitrotoluene (TNT), nitroglycerin (NG), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), pentaerythritol tetranitrate (PETN), triacetone triperoxide (TATP), hexamethylene triperoxide diamine (HMTD), and cyclohexanone, with detection limits in the parts-per-trillion to parts-per-quadrillion range by volume. The instrument can illustrate aspects of vapor plume dynamics, such as detecting plume filaments at a distance. The instrument was deployed to support canine training in the field, detecting cross-contamination among training materials, and developing an evaluation method based on the odor environment. Support for training material production and handling was provided by studying the dynamic headspace of a nonexplosive HMTD training aid that is in development. These results supported existing canine training and identified certain areas that may be improved.

Development of Lu-177-trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients.

HER2/neu is over expressed in 20-25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu-177-trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu-177 with high radiochemical purity (up to 91%) and specific activity (6-13 µCi/µg). Lu-177-trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu-177-trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu-177-trastuzumab. The study demonstrated that in-house developed Lu-177-trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.

A biomarker-responsive T2ex MRI contrast agent.

PURPOSE: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2 exchange (T2ex ) properties after interacting with a molecular biomarker. METHODS: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2 . The R1 and R2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2ex relaxivities. RESULTS: The reaction of Tm-DO3A-oAA with NO and O2 caused a 6.4-fold increase in the r2 relaxivity of the agent, whereas r1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2ex agent. The effects of pH and temperature on the r2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. CONCLUSIONS: T2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665-1670, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Composite glycerol/graphite/aromatic acid matrices for thin-layer chromatography/matrix-assisted laser desorption/ionization mass spectrometry of heterocyclic compounds.

New composite matrices have been suggested for the analysis of mixtures of different synthetic organic compounds (N-containing heterocycles and erectile dysfunction drugs) by thin layer chromatography/matrix-assisted laser desorption ionization time-of-flight mass spectrometry (TLC/MALDI-TOF). Different mixtures of classical MALDI matrices and graphite particles dispersed in glycerol were used for the registration of MALDI mass spectra directly from TLC plates after analytes separation. In most of cases, the mass spectra possessed [M+H]+ ions; however, for some analytes only [M+Na]+ and [M+K]+ ions were observed. These ions have been used to generate visualized TLC chromatograms. The described approach increases the desorption/ionization efficiencies of analytes separated by TLC, prevent spot blurring, simplifies and decrease time for sample preparation.

Dopant-Assisted Positive Photoionization Ion Mobility Spectrometry Coupled with Time-Resolved Thermal Desorption for On-Site Detection of Triacetone Triperoxide and Hexamethylene Trioxide Diamine in Complex Matrices.

Peroxide explosives, such as triacetone triperoxide (TATP) and hexamethylene trioxide diamine (HMTD), were often used in the terrorist attacks due to their easy synthesis from readily starting materials. Therefore, an on-site detection method for TATP and HMTD is urgently needed. Herein, we developed a stand-alone dopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) coupled with time-resolved thermal desorption introduction for rapid and sensitive detection of TATP and HMTD in complex matrices, such as white solids, soft drinks, and cosmetics. Acetone was chosen as the optimal dopant for better separation between reactant ion peaks and product ion peaks as well as higher sensitivity, and the limits of detection (LODs) of TATP and HMTD standard samples were 23.3 and 0.2 ng, respectively. Explosives on the sampling swab were thermally desorbed and carried into the ionization region dynamically within 10 s, and the maximum released concentration of TATP or HMTD could be time-resolved from the matrix interference owing to the different volatility. Furthermore, with the combination of the fast response thermal desorber (within 0.8 s) and the quick data acquisition software to DAPP-IMS, two-dimensional data related to drift time (TATP: 6.98 ms, K0 = 2.05 cm(2) V(-1) s(-1); HMTD: 9.36 ms, K0 = 1.53 cm(2) V(-1) s(-1)) and desorption time was obtained for TATP and HMTD, which is beneficial for their identification in complex matrices.