ABSTRACT
This study, conducted in Debrecen, Hungary, aimed to analyse atmospheric particulate matter (APM or PM) through radiocarbon and PIXE analyses during the winter smog (23-25 January) and spring (15-18 May) seasons. The information presented in this pilot study aims to provide insight into the importance of utilising detailed characteristics of the mass size distributions of fossil carbon (ff) and contemporary carbon (fC) content. Additionally, it seeks to compare these characteristics with the size distributions of various elements to enable even more accurate PM source identification. In winter, APM concentrations were 86.27 µg/m3 (total), 17.07 µg/m3 (fC) and 10.4 µg/m3 (ff). In spring, these values changed to 29.5 µg/m3, 2.64 µg/m3 and 7.01 µg/m3, respectively. Notably, differences in mass size distribution patterns were observed between the two seasons, suggesting varied sources for contemporary carbon. Biomass burning emerged as a crucial source during the smog period, supported by similar MMAD (Mass Median Aerodynamic Diameter) values and a strong correlation (r = 0.95, p < 0.01) between potassium and fC. In spring, a significant change in the concentration and distribution of fC occurred, with a broad, coarse mode and a less prominent accumulation mode. Ff was found to have similar distributions as PM, with nearly the same MMADs, during both periods. Finally, a comprehensive comparison of modal characteristics identified specific sources for the various components, including biomass burning, vehicle exhaust, coal and oil combustion, vehicle non-exhaust, road dust, tyre abrasion, mineral dust and biogenic emission. This study showcases how using radiocarbon and PIXE analysis in size distribution data can enhance our understanding of the sources of PM and their effects on different size fractions of PM.
Subject(s)
Aerosols , Air Pollutants , Environmental Monitoring , Particle Size , Particulate Matter , Aerosols/analysis , Pilot Projects , Air Pollutants/analysis , Particulate Matter/analysis , Environmental Monitoring/methods , Hungary , Seasons , Cities , Carbon Radioisotopes/analysisABSTRACT
This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [52Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [52Mn]Mn isotope. In comparison to DOTA-GA-trastuzumab, the BPPA-trastuzumab conjugate exhibits a labeling efficiency with [52Mn]Mn approximately 2 orders of magnitude higher. In female CB17 SCID mice bearing 4T1 (HER2-) and MDA-MB-HER2+ (HER2+) xenografts, [52Mn]Mn-BPPA-trastuzumab demonstrated superior uptake in HER2+ cells on day 3, with a 3-4 fold difference observed on day 7. Overall, the hexadentate BPPA chelator proves to be exceptional in binding Mn(II). Upon coupling with trastuzumab as a BFC ligand, it becomes an excellent imaging probe for HER2-positive tumors. [52Mn]Mn-BPPA-trastuzumab enables an extended imaging time window and earlier detection of HER2-positive tumors with superior tumor-to-background contrast.
Subject(s)
Manganese , Mice, SCID , Positron-Emission Tomography , Receptor, ErbB-2 , Trastuzumab , Animals , Female , Mice , Cell Line, Tumor , Chelating Agents/chemistry , Chelating Agents/chemical synthesis , Manganese/chemistry , Manganese/metabolism , Mice, Inbred BALB C , Picolinic Acids/chemistry , Positron-Emission Tomography/methods , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Receptor, ErbB-2/metabolism , Tissue Distribution , Trastuzumab/chemistryABSTRACT
BACKGROUND: In this study we evaluated the imaging capabilities of a novel Multi-pinhole collimator (MPH-Cardiac) specially designed for nuclear cardiology imaging on a Triple-NaI-detector based SPECT/CT system. METHODS: 99mTc point source measurements covering the field of view (FOV) were used to determine tomographic sensitivity (TSpointsource) and spatial resolution. Organ-size tomographic sensitivity (TSorgan) was measured with a left ventricle (LV) phantom filled with typical myocardial activity of a patient scan. Reconstructed image uniformity was measured with a 140 mm diameter uniform cylinder phantom. Using the LV phantom once filled with 99mTc and after with 123I, Contrast-to-noise ratio (CNR) was measured on the reconstructed images by ROI analysis on the myocardium activity and on the LV cavity. Furthermore, a polar map analysis was performed determining Spill-Over-Ratio in water (SORwater) and image noise. The results were compared with that of a dual-head parallel-hole low energy high resolution (LEHR) collimator system. A patient with suspected coronary artery disease (CAD) was scanned on the LEHR system using local protocol of 16 min total acquisition time, followed by a 4-min MPH-Cardiac scan. RESULTS: Peak TSpointsource was found to be 1013 cps/MBq in the axial center of the FOV while it was decreasing toward the radial edges. TSorgan in the CFOV was found to be 134 cps/MBq and 700 cps/MBq for the LEHR and MPH-Cardiac, respectively. Average spatial resolution throughout the FOV was 4.38 mm FWHM for the MPH-Cardiac collimator. Reconstructed image uniformity values were found to be 0.292% versus 0.214% for the LEHR and MPH-Cardiac measurements, respectively. CNR was found to be higher in case of MPH-Cardiac than for LEHR in case of 99mTc (15.5 vs. 11.7) as well as for 123I (13.5 vs. 8.3). SORwater values were found to be 28.83% and 21.1% for the 99mTc measurements, and 31.44% and 24.33% for the 123I measurements for LEHR and MPH-Cardiac, respectively. Pixel noise of the 99mTc polar maps resulted in values of 0.38% and 0.24% and of the 123I polar maps 0.62% and 0.21% for LEHR and MPH-Cardiac, respectively. Visually interpreting the patient scan images, MPH-Cardiac resulted in better image contrast compared to the LEHR technique with four times shorter scan duration. CONCLUSIONS: The significant image quality improvement achieved with dedicated MPH-Cardiac collimator on triple head SPECT/CT system paves the way for short acquisition and low-dose cardiovascular SPECT applications.
ABSTRACT
Among humanized monoclonal antibodies, bevacizumab specifically binds to vascular endothelial growth factor A (VEGF-A). VEGF-A is an overexpressed biomarker in cervix carcinoma and is involved in the development and maintenance of tumor-associated neo-angiogenesis. The non-invasive positron emission tomography using radiolabeled target-specific antibodies (immuno-PET) provides the longitudinal and quantitative assessment of tumor target expression. Due to antibodies having a long-circulating time, radioactive metal ions (e.g., 52Mn) with longer half-lives are the best candidates for isotope conjugation. The aim of our preclinical study was to assess the biodistribution and tumor-targeting potential of 52Mn-labeled DOTAGA-bevacizumab. The VEGF-A targeting potential of the new immuno-PET ligand was assessed by using the VEGF-A expressing KB-3-1 (human cervix carcinoma) tumor-bearing CB17 SCID mouse model and in vivo PET/MRI imaging. Due to the high and specific accumulation found in the subcutaneously located experimental cervix carcinoma tumors, [52Mn]Mn-DOTAGA-bevacizumab is a promising PET probe for the detection of VEGF-A positive gynecological tumors, for patient selection, and monitoring the efficacy of therapies targeting angiogenesis.
ABSTRACT
The P-type ATPase CrpA is an important Cu2+ /Cd2+ pump in the Aspergilli, significantly contributing to the heavy metal stress tolerance of these ascomycetous fungi. As expected, the deletion of crpA resulted in Cu2+ /Cd2+ -sensitive phenotypes in Aspergillus nidulans on stress agar plates inoculated with conidia. Nevertheless, paradoxical growth stimulations were observed with the ΔcrpA strain in both standard Cu2+ stress agar plate experiments and cellophane colony harvest (CCH) cultures, when exposed to Cd2+ . These observations reflect efficient compensatory mechanisms for the loss of CrpA operating under these experimental conditions. It is remarkable that the ΔcrpA strain showed a 2.7 times higher Cd biosorption capacity in CCH cultures, which may facilitate the development of new, fungal biomass-based bioremediation technologies to extract harmful Cd2+ ions from the environment. The nullification of crpA also significantly changed the spatial distribution of Cu and Cd in CCH cultures, as demonstrated by the combined particle-induced X-ray emission and scanning transmission ion microscopy technique. Most important, the centers of gravity for Cu and Cd accumulations of the ΔcrpA colonies shifted toward the older regions as compared with wild-type surface cultures.