Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Fate and removal of iodinated X-ray contrast media in membrane bioreactor: Microbial dynamics and effects of different operational parameters.

Iodinated X-ray contrast media (ICM) are mainly used in medical sector, and their presence in environmental waters is a cause of concern as they are capable of forming highly toxic iodinated disinfection byproducts. In the present study, the removal mechanisms of the three ICM- iohexol, iopromide, and iopamidol were elucidated in a lab-scale aerobic membrane bioreactor (MBR). At steady-state operation (solids retention time (SRT)- 70 days, organic loading rate (OLR)- 0.80 KgCOD/m3-day, nitrogen loading rate (NLR)- 0.08 KgNH4-N/m3-day, hydraulic retention time (HRT)- 12 h), the average removal of iohexol and iopromide was found to be 34.9 and 45.2 %, respectively, whereas iopamidol proved to be highly recalcitrant in aerobic conditions of the MBR (removal <10 % in all phases of the MBR operation). Further, through batch kinetic studies and mass balance analysis, it was observed that ICM were primarily biotransformed in the MBR system and biosorption (Kd < 10 L/Kg) was negligible. The biodegradation rate coefficient values (Kbiol) of the ICM were found to be <0.65 L/g-d which indicate that biotransformation rate of ICM was slow. Increased OLR (1.60 KgCOD/m3-day) and reduced SRT (20 days) were found to negatively affect the removal of the ICM. Further, the removal of ICM was found to depend on its initial concentration, and the increment in the ammonium loading (0.16 KgNH4-N/m3-day) did not favor its removal. The dosing of ICM altered the microbial dynamics of the mixed liquor and reduced the microbial diversity and richness. Bdellovibrio, Zoogloea, and bacteria belonging to TM7-3 class, Cryomorphaceae and Hyphomonadaceae families may contribute in ICM biotransformation.

Comparison of different analytical methods for speciation of seven gadolinium-based magnetic resonance imaging contrast agents and the applications in wastewater and whole blood.

Three methods, high-performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry, high-performance liquid chromatography-tandem mass spectrometry, and ion chromatography, were compared for simultaneous speciation of seven commercial gadolinium-based contrast agents for magnetic resonance imaging. Optimizations of experimental conditions for individual method were conducted, respectively. Methods of high-performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry showed the capability of speciation for all seven target compounds, whereas ion chromatography was only suitable for three of them when using electronic conductivity detector. The limits of detection and limits of qualification by the three methods were compared, and high-performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry was found to be the most sensitive one. The limits of detection for seven target compounds by high-performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry were in the range of 0.15-0.55 pg. Thus, high-performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry was chosen as the final method and successfully applied to speciation analysis of seven gadolinium-based contrast agents in wastewater and whole blood. Compounds of gadoxetic acid disodium, gadobenate dimeglumine, gadodiamide, and gadobentetate dimeglumine were found in wastewater.

Future in precise surgery: Fluorescence-guided surgery using EVs derived fluorescence contrast agent.

Surgery is the only cure for many solid tumors, but positive resection margins, damage to vital nerves, vessels and organs during surgery, and the range and extent of lymph node dissection are significant concerns which hinder the development of surgery. The emergence of fluorescence-guided surgery (FGS) means a farewell to the era when surgeons relied only on visual and tactile feedback, and it gives surgeons another eye to distinguish tumors from normal tissues for precise resection and helps to find a balance between complete tumor lesions removal and maximal organ function conservation. However, the existing synthetic fluorescence contrast agent has flaws in safety, specificity and biocompatibility to various extents. Extracellular vesicles (EVs) are a group of heterogeneous types of cell-derived membranous structures present in all biological fluids. EVs, especially engineered targeting EVs, play an increasingly important role in drug delivery because of their good biocompatibility, validated safety and targeting ability. Nevertheless, few studies have employed EVs loaded with fluorophores to construct fluorescence contrast agents and used them in FGS. Here, we systematically reviewed the current state of knowledge regarding FGS, fundamental characteristics of EVs, and the development of engineered targeting EVs, and put forward a novel strategy and procedures to produce EVs-based fluorescence contrast agent used in fluorescence-guided surgery.

Evaluation of the accumulation of the iodinated contrast agents diatrizoic acid and iohexol in Dreissena polymorpha mollusks.

Mollusks are very sensitive to aquatic environmental alterations and then, are important bio-indicators for monitoring the contamination of water bodies. Iodinated X-ray contrast media (ICMs) are ubiquitously present in the aquatic environment, primarily due to their high consumption for diagnosis purposes, high injection levels, low biodegradability, and low removal rates by wastewater treatment plants. Although these compounds are assumed to be of low toxicity, aquatic organisms are continuously exposed to these agents, which may result in adverse effects as ICMs can act as iodine source and disrupt the endocrine system. Thus, the evaluation of their environmental risk, especially on aquatic fauna is of great interest. To this end, we first compared the accumulation behavior, based on iodine analysis, of two ICM exhibiting different osmolality, diatrizoic acid and iohexol in Dreissena polymorpha bivalves exposed under laboratory conditions at concentrations of 0, 100, and 1000 µg/L during 4 and 7 days. This study was the first to provide information on iodine concentration in whole soft tissues and several organs in control zebra mussels. Moreover, it showed, after exposure, an increase of iodine content mainly in the digestive glands, followed by gills and gonads, highlighting that ICMs actually enter the organisms. Thus, bioaccumulation of ICMs studies were then performed, by liquid chromatography coupled to tandem mass spectrometry, on entire mollusks and digestive glands of organisms exposed at 0, 10, 100, and 1000 µg/L of both ICMs during 21 days, followed by 4 days of depuration. These first data on ICMs concentrations in zebra mussels, showed a clear accumulation of ICMs in mussels as a function of relative exposure level, as well as a rapid depuration. Osmolality did not seem to have a significant impact on the accumulation level, but a slight difference was observed on the accumulation pattern between both ICMs.

Assessing the skin irritation and sensitizing potential of concentrates of water chlorinated in the presence of iodinated X-ray contrast media.

Chemical disinfection of water provides significant public health benefits. However, disinfectants like chlorine can react with naturally occurring materials in the water to form disinfection byproducts (DBPs). Natural levels of iodine have been reported to be too low in some source waters to account for the levels of iodinated DBPs detected. Iodinated X-ray contrast media (ICM) have been identified as a potential source of iodine. The toxicological impact of ICM present in source water at the time of disinfection has not been fully investigated. Iopamidol, iohexol, iopromide, and diatrizoate are among the ICM most frequently detected in water. In this study, source water containing one of these four ICM was chlorinated; non-chlorinated ICM-containing water samples served as controls. Reactions were conducted at an ICM concentration of 5 µM and a chlorine dose of 100 µM over 72 hr. Water concentrates (20,000-fold) were prepared by XAD-resin/ethyl acetate extraction and DMSO solvent exchange. We used the MatTek® reconstituted human epithelial skin irritation model to evaluate the water concentrates and also assessed the dermal irritation and sensitization potential of these concentrates using the LLNA:BrdU ELISA in BALB/c mice. None of the water concentrates tested (2500X) resulted in a skin irritant response in the MatTek® skin irritation model. Likewise, none of the concentrates (2500X, 1250X, 625X, 312.5X, 156.25X) produced a skin irritation response in mice: erythema was minimal; the maximum increase in ear thickness was less than 25%. Importantly, none of the concentrates produced a positive threshold response for allergic skin sensitization at any concentration tested in the LLNA:BrdU ELISA. We conclude that concentrates of water disinfected in the presence of four different ICM did not cause significant skin irritation or effects consistent with skin sensitization at the concentrations tested.

Magnetic Particle Imaging of Magnetotactic Bacteria as Living Contrast Agents Is Improved by Altering Magnetosome Arrangement.

Superparamagnetic iron oxide nanoparticles (SPIONs) can be used as imaging agents to differentiate between normal and diseased tissue or track cell movement. Magnetic particle imaging (MPI) detects the magnetic properties of SPIONs, providing quantitative and sensitive image data. MPI performance depends on the size, structure, and composition of nanoparticles. Magnetotactic bacteria produce magnetosomes with properties similar to those of synthetic nanoparticles, and these can be modified by mutating biosynthetic genes. The use of Magnetospirillum gryphiswaldense, MSR-1 with a mamJ deletion, containing clustered magnetosomes instead of typical linear chains, resulted in improved MPI signal and resolution. Bioluminescent MSR-1 with the mamJ deletion were administered into tumor-bearing and healthy mice. In vivo bioluminescence imaging revealed the viability of MSR-1, and MPI detected signals in livers and tumors. The development of living contrast agents offers opportunities for imaging and therapy with multimodality imaging guiding development of these agents by tracking the location, viability, and resulting biological effects.

Healthy US population reference values for CT visceral fat measurements and the impact of IV contrast, HU range, and spinal levels.

Measurements of visceral adipose tissue cross-sectional area and radiation attenuation from computed tomography (CT) scans provide useful information about risk and mortality. However, scan protocols vary, encompassing differing vertebra levels and utilizing differing phases of contrast enhancement. Furthermore, fat measurements have been extracted from CT using different Hounsfield Unit (HU) ranges. To our knowledge, there have been no large studies of healthy cohorts that reported reference values for visceral fat area and radiation attenuation at multiple vertebra levels, for different contrast phases, and using different fat HU ranges. Two-phase CT scans from 1,677 healthy, adult kidney donors (age 18-65) between 1999 and 2017, previously studied to determine healthy reference values for skeletal muscle measures, were utilized. Visceral adipose tissue cross-sectional area (VFA) and radiation attenuation (VFRA) measures were quantified using axial slices at T10 through L4 vertebra levels. T-tests were used to compare males and females, while paired t-tests were conducted to determine the effect (magnitude and direction) of (a) contrast enhancement and (b) different fat HU ranges on each fat measure at each vertebra level. We report the means, standard deviations, and effect sizes of contrast enhancement and fat HU range. Male and female VFA and VFRA were significantly different at all vertebra levels in both contrast and non-contrast scans. Peak VFA was observed at L4 in females and L2 in males, while peak VFRA was observed at L1 in both females and males. In general, non-contrast scans showed significantly greater VFA and VFRA compared to contrast scans. The average paired difference due to contrast ranged from 1.6 to - 8% (VFA) and 3.2 to - 3.0% (VFRA) of the non-contrast value. HU range showed much greater differences in VFA and VFRA than contrast. The average paired differences due to HU range ranged from - 5.3 to 22.2% (VFA) and - 5.9 to 13.6% (VFRA) in non-contrast scans, and - 4.4 to 20.2% (VFA) and - 4.1 to 12.6% (VFRA) in contrast scans. The - 190 to - 30 HU range showed the largest differences in both VFA (10.8% to 22.2%) and VFRA (7.6% to 13.6%) compared to the reference range (- 205 to - 51 HU). Incidentally, we found that differences in lung inflation result in very large differences in visceral fat measures, particularly in the thoracic region. We assessed the independent effects of contrast presence and fat HU ranges on visceral fat cross-sectional area and mean radiation attenuation, finding significant differences particularly between different fat HU ranges. These results demonstrate that CT measurements of visceral fat area and radiation attenuation are strongly dependent upon contrast presence, fat HU range, sex, breath cycle, and vertebra level of measurement. We quantified contrast and non-contrast reference values separately for males and females, using different fat HU ranges, for lumbar and thoracic CT visceral fat measures at multiple vertebra levels in a healthy adult US population.

11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans.

Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

Administration of a VEGFR­2-specific MRI contrast agent to assess orthodontic tooth movement : A pilot study.

PURPOSE: It is thought that orthodontic forces initially reduce periodontal blood flow during orthodontic tooth movement (OTM) via tissue compression with cells responding to concomitant oxygen deprivation with expression of vascular endothelial growth factor (VEGF) triggering angiogenesis via binding to its receptor VEGFR­2. To test this hypothesis, we performed a pilot study to establish a protocol for molecular magnetic resonance imaging (MRI) of rat jaws administering a VEGFR-2-specific contrast agent. METHODS: Mesial OTM of a first upper left rat molar was initiated in one male Fischer 344 rat 4 days prior to MRI by insertion of an elastic band between the first and second upper molars with the contralateral side left untreated (internal control). T1-weighted MRI sequences including dynamic contrast-enhanced MRI (DCE-MRI) were recorded before and after administration of a molecular VEGFR­2 MRI marker with a 7 T MRI dedicated for small animal use. RESULTS: After injection of anti-VEGFR2-albumin-gadolinium-DTPA, volume enhancement on T1-weighted images was increased at the OTM side distally of the moved first upper molar (M1) compared to the control side, whereas the T1 relaxation time was reduced on the OTM side. DCE-MRI resulted in an increased area under the curve (AUC), whereas time-to-peak (TTP) and washout rate were reduced during OTM distally of the moved M1 compared to the contralateral side. CONCLUSIONS: OTM resulted in uptake of the VEGFR-2-specific MRI contrast agent in tension areas of the periodontal ligament. The imaging protocol presented here is useful for the assessment of VEGFR­2 expression in tension areas of the periodontal ligament in vivo.

Effect of formalin fixation on measured concentrations of deposited gadolinium in human tissue: an autopsy study.

BACKGROUND: Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated. PURPOSE: To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues. MATERIAL AND METHODS: Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS. RESULTS: Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation (P = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month (P = 0.11) and 6.0% (P = 0.73) between one and three months. CONCLUSION: Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%-40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.

Assessing the reproducibility of high temporal and spatial resolution dynamic contrast-enhanced magnetic resonance imaging in patients with gliomas.

Temporal and spatial resolution of dynamic contrast-enhanced MR imaging (DCE-MRI) is critical to reproducibility, and the reproducibility of high-resolution (HR) DCE-MRI was evaluated. Thirty consecutive patients suspected to have brain tumors were prospectively enrolled with written informed consent. All patients underwent both HR-DCE (voxel size, 1.1 × 1.1 × 1.1 mm3; scan interval, 1.6 s) and conventional DCE (C-DCE; voxel size, 1.25 × 1.25 × 3.0 mm3; scan interval, 4.0 s) MRI. Regions of interests (ROIs) for enhancing lesions were segmented twice in each patient with glioblastoma (n = 7) to calculate DCE parameters (Ktrans, Vp, and Ve). Intraclass correlation coefficients (ICCs) of DCE parameters were obtained. In patients with gliomas (n = 25), arterial input functions (AIFs) and DCE parameters derived from T2 hyperintense lesions were obtained, and DCE parameters were compared according to WHO grades. ICCs of HR-DCE parameters were good to excellent (0.84-0.95), and ICCs of C-DCE parameters were moderate to excellent (0.66-0.96). Maximal signal intensity and wash-in slope of AIFs from HR-DCE MRI were significantly greater than those from C-DCE MRI (31.85 vs. 7.09 and 2.14 vs. 0.63; p < 0.001). Both 95th percentile Ktrans and Ve from HR-DCE and C-DCE MRI could differentiate grade 4 from grade 2 and 3 gliomas (p < 0.05). In conclusion, HR-DCE parameters generally showed better reproducibility than C-DCE parameters, and HR-DCE MRI provided better quality of AIFs.

Background-Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation.

We report on the utility of Radiofrequency Amplification by Stimulated Emission Radiation (RASER) for background-free proton detection of hyperpolarized biomolecules. We performed hyperpolarization of ≈0.3 M ethyl acetate via pairwise parahydrogen addition to vinyl acetate. A proton NMR signal with signal-to-noise ratio exceeding 100 000 was detected without radio-frequency excitation at the clinically relevant magnetic field of 1.4 T using a standard (non-cryogenic) inductive detector with quality factor of Q=68. No proton background signal was observed from protonated solvent (methanol) or other added co-solvents such as ethanol, water or bovine serum. Moreover, we demonstrate RASER detection without radio-frequency excitation of a bolus of hyperpolarized contrast agent in biological fluid. Completely background-free proton detection of hyperpolarized contrast agents in biological media paves the way to new applications in the areas of high-resolution NMR spectroscopy and in vivo spectroscopy and imaging.

Visualization of the renal vein filled with contrast agent may indicate the renal vein injury during percutaneous nephrolithotomy: two case reports.

BACKGROUND: Intravenous misplacement of a nephrostomy tube is a rare complication of percutaneous nephrolithotomy (PCNL) or percutaneous nephrostomy. The mechanism of misplacement of a nephrostomy tube into the vascular system is seldom investigated. One type of the possible mechanism is that the puncture needle penetrates a major intrarenal tributary of the renal vein and enters the collecting system. However, the guidewire is located outside the collecting system near the large branches of renal vein or perforates into the renal vein. The dilation is performed and causes a large torn injury. Subsequently, the nephrostomy tube is placed inside the vessel when radiological monitoring is not used. However, there is no imaging evidence and the scene of procedure is not demonstrated. This paper reports two cases of visualization of the renal vein filled with contrast agent during PCNL. The findings may be good evidence to support the step of renal vein injury in patients with intravenous nephrostomy tube misplacement. CASE PRESENTATION: We presented two cases with visualization of the renal vein filled with contrast agent during PCNL. In the process of injecting the contrast agent through the puncture needle, we could see the renal vein. Moreover, it was identified that the puncture needle tip was not on the optimal position. The position of puncture needle tip lay outside the collecting system, which was close to the calyceal infundibulum and branches of renal vein. CONCLUSIONS: Visualization of the renal vein filled with contrast agent may be good evidence to verify the renal vein injury in patients with intravenous nephrostomy tube misplacement during PCNL or percutaneous nephrostomy. The suboptimal location of the puncture needle tip and visualization of the renal vein filled with contrast agent indicate the renal vein injury. One type of mechanism of intravenous nephrostomy tube misplacement is as following. Firstly, the guidewire stays outside the collecting system. Subsequently, dilatation directed by the guidewire results in the injury of the vein. Then, the nephrostomy tube migrates into the venous system due to prompt tube inserting and the direction of the sheath and/or the guidewire to the injured vein.

Single Fluorinated Agent for Multiplexed 19 F-MRI with Micromolar Detectability Based on Dynamic Exchange.

The weak thermal polarization of nuclear spins limits the sensitivity of MRI, even for MR-sensitive nuclei as fluorine-19. Therefore, despite being the source of inspiration for the development of background-free MRI for various applications, including for multiplexed imaging, the inability to map very low concentrations of targets using 19 F-MRI raises the need to further enhance this platform's capabilities. Here, we employ the principles of CEST-MRI in 19 F-MRI to obtain a 900-fold signal amplification of a biocompatible fluorinated agent, which can be presented in a "multicolor" fashion. Capitalizing on the dynamic interactions in host-guest supramolecular assemblies in an approach termed GEST, we demonstrate that an inhalable fluorinated anesthetic can be used as a single 19 F-probe for the concurrent detection of micromolar levels of two targets, with potential in vivo translatability. Further extending GEST with new designs could expand the applicability of 19 F-MRI to the mapping of targets that have so-far remained non-detectable.

Description of a novel ultrasound guided peribulbar block in horses: a cadaveric study.

BACKGROUND: Standing surgery in horses combining intravenous sedatives, analgesics and local anaesthesia is becoming more popular. Ultrasound guided (USG) peribulbar nerve block (PB) has been described in dogs and humans for facial and ocular surgery, reducing the risk of complications versus retrobulbar nerve block (RB). OBJECTIVE: To describe a technique for USG PB in horse cadavers. METHODS: Landmarks and PB technique were described in two equine cadaver heads (Phase 1), with computed tomography (CT) imaging confirming contrast location and spread. In Phase 2, ten equine cadaver heads were randomised to two operators naïve to the USG PB, with moderate experience with ultrasonography and conventional "blind" RB. Both techniques were demonstrated once. Subsequently, operators performed five USG PB and five RB each, unassisted. Contrast location and spread were evaluated by CT. Injection site success was defined for USG PB as extraconal contrast, and for RB intraconal contrast. RESULTS: Success was 10/10 for USG PB and 0/10 for RB (p < 0.001). Of the RB injections, eight resulted in extraconal contrast and two in the masseter muscle (p = 0.47). CONCLUSIONS: The USG PB had a high injection site success rate compared with the RB technique; however, we cannot comment on clinical effect. The USG technique was easily learnt, and no potential complications were seen. The USG PB nerve block could have a wide application for use in horses for ocular surgeries (enucleations, eyelid, corneal, cataract surgeries, and ocular analgesia) due to reduced risk of iatrogenic damage. Further clinical studies are needed.

Molecular imaging of orthotopic prostate cancer with nanobubble ultrasound contrast agents targeted to PSMA.

Ultrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice. Our results demonstrated that PSMA-targeted NBs had increased extravasation and retention in PSMA-expressing orthotopic mouse tumors. These processes are reflected in significantly different time intensity curve (TIC) and several kinetic parameters for targeted versus non-targeted NBs or LUMASON MBs. These, may in turn, lead to improved image-based detection and diagnosis of PCa in the future.

Variability in hair gadolinium concentrations among decedents who received gadolinium-based contrast agents.

This study utilized laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify gadolinium in the hair of autopsy cases that had received gadolinium-based contrast agents (GBCAs) before death. Consecutive autopsy cases were reviewed for GBCA injections and subjects who received a single type of GBCA in the year before death were included. Hair samples were analyzed using LA-ICP-MS as a line scan technique and parameters were optimized to maximize instrument sensitivity, accuracy, and precision. Linear regression analyses between hair measures and gadolinium dose were executed. LA-ICP-MS analysis produced a time-resolved record of GCBA exposure, with the position of the gadolinium peak maxima along the hair shaft providing a good estimate for the day that GBCA injection occurred (R2 = 0.46; p = 0.0022); however, substantial within and between subject variation in the position of the GBCA peak was observed. Average area under the curve for gadolinium peaks in the hair samples was a better predictor of gadolinium dose (R2 = 0.41; p = 0.0046), compared to the average of peak maxima concentration. Correlation between area under the curve and dose suggests that LA-ICP-MS analysis of hair may be an effective method to evaluate gadolinium levels in subjects in vivo after exposure to GBCAs. This study demonstrates that analysis of human hair using techniques with high spatial resolution such as LA-ICP-MS has excellent potential to reveal time-dependent signatures of past exposures.