David Aebisher

19F applications in drug development and imaging – a review

To control drugs in vivo, new approaches are needed. Considerable progress has been made towards the applications of fluorine ((19)F) in pharmacotherapy in this regard. To date, many authors have showed that by using (19)F labelled drugs and non-invasive magnetic resonance imaging (MRI) techniques together, drug biodistribution can be tracked. This review presents methods for (19)F incorporation into pharmaceuticals by forming C-F bonds and drug fluorine oil-water emulsions. Inadequate drug delivery is a major cause of drug resistance, which can be improved using approaches discussed herein aided by (19)F MRI.

Laser flow cytometry as a tool for the advancement of clinical medicine

Flow cytometry is a classic laser technology. With the discovery of the cytometer, flow cytometry has become a primary tool in biodiagnostic research. This review focuses on current applications of flow cytometry to the diagnosis of disease and treatment monitoring at the single-cell level. A description of the principles of flow cytometry and a brief overview of the major applications are presented. Our criteria for selecting research papers for this review are those that show advances in biomedicine and pharmacotherapy achieved by using non-invasive flow cytometry. New concepts for diagnosis and classification based on quantitative measurements of cellular parameters and the expression of specific differentiation antigens on the surface of cells will be discussed herein.

A review of new approaches in Her-2 targeting and 1H MRI application

To date, the Her-2 receptor is the most frequently detected breast cancer biomarker which can be monitored on the surface of tumors by proton magnetic resonance imaging (1H MRI). In the past decade, we observed major advances in the development of 1H MRI as a diagnostic tool in cancer studies. 1H MRI is noninvasive method and can be used to explore tumor biology, cancer cell surface morphology and provide information about drug efficacy, absorption, distribution, and elimination. This review describes current studies of Her-2 targeting with trastuzumab and the application of 1H MRI to Her-2 receptor detection.

Effects of androsterone on the protective action of various antiepileptic drugs against maximal electroshock-induced seizures in mice

This study evaluated the effect of androsterone (AND), a metabolite of testosterone, on the ability of selected classical and novel antiepileptic drugs to prevent seizures caused by maximal electroshock (MES), which may serve as an experimental model of human generalized tonic-clonic seizures in mice. Single intraperitoneal (i.p.) administration of AND (80 mg kg-1) significantly raised the threshold for convulsions in the MES seizure threshold test. Lower doses of AND (5, 10, 20, and 40 mg kg-1) failed to change the threshold. AND at a subthreshold dose of 40 mg kg-1 significantly enhanced the protective activity of carbamazepine, gabapentin, and phenobarbital against MES-induced seizures decreasing their median effective doses (ED50) values ± SEM from 8.59 ± 0.76 to 6.05 ± 0.81 mg kg-1 (p = 0.0308) for carbamazepine, from 419.9 ± 120.6 to 111.5 ± 41.1 mg kg-1 (p = 0.0405) for gabapentin, and from 20.86 ± 1.64 to 10.0 ± 1.21 mg kg-1 (p = 0.0007) for phenobarbital. There were no significant changes in total brain concentrations of carbamazepine, gabapentin, and phenobarbital following AND administration. This suggests that the enhancing effects of AND on the protective activity of these antiepileptic drugs are not related to pharmacokinetic factors. A lower dose of AND (20 mg kg-1) had no effect on the protective activity of carbamazepine, gabapentin, and phenobarbital. AND administered at a dose of 40 mg kg-1 failed to change the anticonvulsant activity of lamotrigine, oxcarbazepine, phenytoin, topiramate, and valproate in the MES test. In the chimney test, AND given at a dose enhancing the protective activity of carbamazepine, gabapentin, and phenobarbital (which alone was without effect on motor performance of mice) did not affect impairment of motor coordination produced by the antiepileptics. Our findings recommend further preclinical and clinical research on AND in respect of its use as adjuvant therapy in the management of epilepsy in men with deficiency of androgens.

Trastuzumab drug delivery systems for magnetic resonance imaging detection

Abstract The main objective of this chapter is to investigate the utility of trastuzumab conjugates as targeting drug delivery systems. Trastuzumab is a monoclonal antibody used to target the Her2 receptor which overexpresses in breast cancer tissue. Drug delivery systems have utility in cancer targeting where precision of drug delivery to the target is needed. The specific tasks we are going to review in this chapter are: (1) development of the trastuzumab delivery system by synthesis; (2) evaluation of trastuzumab drug delivery systems using magnetic resonance imaging (MRI) and MR spectroscopy (MRS); (3) discussion of the pharmaceutical efficiency of trastuzumab drug delivery systems; and (4) other immunotherapeuticals currently used, which have potential to be used in drug delivery systems. The main rationale of this study is to investigate the utility of 1H/19F MRI and 1H/19F MRS on the tracking and visualization of trastuzumab conjugates on the cellular level. The strategies and methodologies discussed in this chapter present the ability to visualize drug uptake by cancer tissue and to quantify the response of tissue to treatment. The current limitations of antibody immunotherapy, such as quantitative visualization of targeted surface antigens, will be also discussed. This chapter will also review new drug delivery systems which impact drug resistance and human health.

The significance of NGAL and KIM-1 proteins for diagnosis of acute kidney injury (AKI) in clinical practice

Introduction. Despite advances in medical care AKI (acute kidney injury) is associated with high morbidity and mortality. The lack of adequate early renal injury biomarkers is often a problem for an early AKI diagnosis. In recent years, numerous scientific studies have been carried out which reveal new urine and serum markers to assess the period of the kidney injury before revealing its late clinical effects. In most clinical settings, AKI is due to acute renal tubular necrosis which results in protein accumulation in urine. Determination of the concentrations of proteins such as NGAL (neutrophil gelatinase-associated lipocalin) and KIM-1 (kidney injury molecule-1) are of great significance in the diagnosis of AKI. Aim. The purpose of the study was to review the literature about significance of NGAL and KIM-1 proteins for diagnosis of acute kidney injury (AKI) in clinical practice. Materials and method. Analysis of Polish and foreign literature.

Chapter 11 – Applications of 19F Magnetic Resonance Spectroscopy and Imaging for the Study of Nanostructures Used in Antimicrobial Therapy

Abstract The use of nanotechnology in antimicrobial therapy has led to improvements in the treatment of targeted tissue. 19F magnetic resonance spectroscopy (19F MRS) and imaging (19F MRI) offer essential tools for the tracking of fluorine-containing compounds in several critical disease treatments including infectious diseases. Moreover, both techniques are able to provide information about the structure of 19F-containing nanomaterials and monitor the progress of treatment. In addition, a representative number of fluorine-containing compounds are synthesized by the use of bacteria and the analysis of fluorination has been aided by 19F nuclear magnetic resonance (19F NMR), in particular liquid state 19F NMR. In this review, we summarize diagnostic and therapeutic applications of 19F MRS and 19F MRI techniques to nanomedicine in antimicrobial therapy. We provide an overview of the known examples of the synthesis of fluorine-containing compounds by the use of bacteria species and their analysis by 19F NMR.

Differential of live and dead cells by magnetic resonance imaging

Methods to distinguish live and dead cells in vivo are of great interest to medicinal chemistry research. This review summarizes articles describing the use of magnetic resonance imaging for discriminating between live and dead cells. Studies from the perspective of clinical applications were selected for the review.

Functional MRI – how does it work?

Magnetic Nuclear Resonance (MRI) is a non-invasive tissue imaging method. This technique is based on the influence of a strong magnetic field and electromagnetic wave of strictly defined frequency on the nucleus of elements with non-zero spin. The study describes one of the variants of functional MRI, (fMRI), which has become a key technique in brain imaging. This technique has excellent spatial and temporal resolution and involves a changing signal intensity depending on the degree of oxygenation of the blood. Blood oxygenation levels are known to vary in accordance with neural activity and these differences can be used to detect brain activity. This is due to increased demand for energy and oxygen in the area of increased neural activity. The basis of this imaging is the so-called Blood Oxygenation-Level Dependent (BLOD) effect. The aim of this paper is to present the scope of fMRI as a diagnostic method in neurology and in neurosurgery. This paper presents the principles of fMRI, methods of application, research result development, and suggests areas of possible medical applications. The limitations of fMRI as a clinical tool in medical applications will also be addressed. Studies presented in this paper are based on clinical fMRI experience and a literature review.

ASL (Arterial Spin Labeling) – historical and current perfusion MR methods

Despite continuous scientific and technological advances in MR imaging, MR perfusion methods have not yet been widely deployed for routine clinical diagnostics. This is especially true for ASL (arterial spin labelling) methods used to evaluate cerebral perfusion. This method does not require a contrast agent, as new discoveries about gadolinium accumulation in the cerebellum and brain nucleus appear to be a valuable asset and provide the opportunity to be more widely deployed in clinical practice. The aim of this paper is to present the historical determinants of the development of MR perfusion techniques, the disadvantages and advantages and possible clinical applications and prospects of ASL development. Both historical articles published on MR in the 1990s and current research between 2006-2016 have been reviewed. The authors present in the work the MR perfusion method focusing on issues related to arterial spin labeling (ASL). Historically CASL (continuous ASL) and PCSL (pulsed ASL) techniques have been described and the pseudocontinuous ASL (pseudocontinuous ASL) 3D technique presents its technical and methodological considerations, advantages and disadvantages over previous methods. The methods of test protocol optimization and accompanying artifacts, as well as possible clinical applications and development perspectives, have been