The design and preclinical evaluation of a single-label bimodal nanobody tracer for image-guided surgery

Intraoperative guidance using targeted fluorescent tracers can potentially provide surgeons with real-time feedback on the presence of tumor tissue in resection margins. To overcome the limited depth penetration of fluorescent light, combining fluorescence with SPECT/CT imaging and/or gamma-ray tracing has been proposed. Here, we describe the design and preclinical validation of a novel bimodal nanobody-tracer, labeled using a "multifunctional single attachment point" (MSAP) label, integrating a Cy5 fluorophore and a diethylenetriaminepentaacetic acid (DTPA) chelator into a single structure. After conjugation of the bimodal MSAP to primary amines of the anti-HER2 nanobody 2Rs15d and In-111-labeling of DTPA, the tracer's characteristics were evaluated in vitro. Subsequently, its biodistribution and tumor targeting were assessed by SPECT/CT and fluorescence imaging over 24 h. Finally, the tracer's ability to identify small, disseminated tumor lesions was investigated in mice bearing HER2-overexpressing SKOV3.IP1 peritoneal lesions. [In-111]In-MSAP.2Rs15d retained its affinity following conjugation and remained stable for 24 h. In vivo SPECT/CT and fluorescence images showed specific uptake in HER2-overexpressing tumors with low background. High tumor-to-muscle ratios were obtained at 1h p.i. and remained 19-fold on SPECT/CT and 3-fold on fluorescence images over 24 h. In the intraperitoneally disseminated model, the tracer allowed detection of larger lesions via nuclear imaging, while fluorescence enabled accurate removal of submillimeter lesions. Bimodal nuclear/fluorescent nanobody-tracers can thus be conveniently designed by conjugation of a single-molecule MSAP-reagent carrying a fluorophore and chelator for radioactive labeling. Such tracers hold promise for clinical applications.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Laparoscopic artificial urinary sphincter in women for type III incontinence: preliminary results.

PURPOSE: To evaluate the feasibility by laparoscopy of the AMS 800 (American Medical Systems, Inc., Minnetonka, Minnesota) artificial urinary sphincter in women with type III incontinence. MATERIALS AND METHODS: Four women with genuine stress incontinence due to intrinsic sphincter deficiency were operated by laparoscopy. Primary criterion was negative Marshall test. One patient had not undergone surgery, and we performed laparoscopic promonto-fixation in the same procedure. Two of the three remaining patients had previous TVT (tension-free vaginal tape) with complications regarding the perforation and erosion of bladder mucosa and urethra. Laparoscopic explantation of TVT was performed 3 months previously. In the last case, previous urethropexy and laparoscopic promonto-fixation in association with TVT were performed 10 years and 1 year ago respectively. A modified surgical procedure was used to implant the AMS 800 through laparoscopic transperitoneal approach, with placement of the cuff around the bladder neck between the periurethral fascia and the vagina. RESULTS: Mean age was 68.5 (50-79) years. Mean closure pressure was 24.5 (20-28) cm. Water. There was no erosion or extrusion. The only significant risk factor was previous surgery. The operative time was less than 3 hours. The hospital stay was 8 days. The mean follow-up was 6 (3-13) months. Activation was done 6 to 8 weeks after implantation. Social continence (1 pad use with moderate leakage) and improvement of quality of life was reported in one patient. In this case the balloon was changed in order to obtain more pressure in the cuff. Resolution of incontinence was achieved in 3 patients. CONCLUSIONS: The AMS 800 can be successfully implanted by laparoscopy to treat women with genuine stress incontinence, a low urethral closure pressure and negative Marshall test indicating severe intrinsic sphincter deficiency. A long term follow-up is warranted to determine the efficacy and durability of this procedure

Solvent effects on IR and VCD spectra of natural products: an experimental and theoretical VCD study of pulegone

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Hybrid-type strigolactone analogues derived from auxins

Contains fulltext : 207484.pdf (Publisher’s version ) (Open Access)9 p

Low efficacy of cardioversion of persistent atrial fibrillation with the implantable cardioverter-defibrillator

AIMS: Atrial fibrillation (AF) and heart failure are conditions that often coexist. Consequently, many patients with an implantable cardioverter-defibrillator (ICD) present with AF. We evaluated the effectiveness of internal cardioversion of AF in patients with an ICD. METHODS: Retrospectively, we included 27 consecutive ICD patients with persistent AF who underwent internal cardioversion using the ICD. When ICD cardioversion failed, external cardioversion was performed. RESULTS: Patients were predominantly male (89 %) with a mean (SD) age of 65 ± 9 years and left ventricular ejection fraction of 36 ± 17 %. Only nine (33 %) patients had successful internal cardioversion after one, two or three shocks. The remaining 18 patients underwent external cardioversion after they failed internal cardioversion, which resulted in sinus rhythm in all. A smaller left atrial volume (99 ± 36 ml vs. 146 ± 44 ml; p = 0.019), a longer right atrial cycle length (227 (186–255) vs. 169 (152–183) ms, p = 0.030), a shorter total AF history (2 (0–17) months vs. 40 (5–75) months, p = 0.025) and dual-coil ICD shock (75 % vs. 26 %, p = 0.093) were associated with successful ICD cardioversion. CONCLUSION: Internal cardioversion of AF in ICD patients has a low success rate but may be attempted in those with small atria, a long right atrial fibrillatory cycle length and a short total AF history, especially when a dual-coil ICD is present. Otherwise, it seems reasonable to prefer external over internal cardioversion when it comes to termination of persistent AF