Structural properties of magnetic nanoparticles determine their heating behavior - an estimation of the in vivo heating potential

Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimally invasive tool for localized tumor treatment by sensitizing or killing tumor cells with the help of thermal stress. Therefore, the selection of MNP exhibiting a sufficient heating capacity (specific absorption rate, SAR) to achieve satisfactory temperatures in vivo is necessary. Up to now, the SAR of MNP is mainly determined using ferrofluidic suspensions and may distinctly differ from the SAR in vivo due to immobilization of MNP in tissues and cells. The aim of our investigations was to study the correlation between the SAR and the degree of MNP immobilization in dependence of their physicochemical features. In this study, the included MNP exhibited varying physicochemical properties and were either made up of single cores or multicores. Whereas the single core MNP exhibited a core size of approximately 15 nm, the multicore MNP consisted of multiple smaller single cores (5 to 15 nm) with 65 to 175 nm diameter in total. Furthermore, different MNP coatings, including dimercaptosuccinic acid (DMSA), polyacrylic acid (PAA), polyethylenglycol (PEG), and starch, wereinvestigated. SAR values were determined after the suspension of MNP in water. MNP immobilization in tissues was simulated with 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels. The highest SAR values were observed in ferrofluidic suspensions, whereas a strong reduction of the SAR after the immobilization of MNP with PVA was found. Generally, PVA embedment led to a higher immobilization of MNP compared to immobilization in agarose gels. The investigated single core MNP exhibited higher SAR values than the multicore MNP of the same core size within the used magnetic field parameters. Multicore MNP manufactured via different synthesis routes (fluidMAG-D, fluidMAG/12-D) showed different SAR although they exhibited comparable core and hydrodynamic sizes. Additionally, no correlation between ζ-potential and SAR values after immobilization was observed. Our data show that immobilization of MNP, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNP are immobilized in cells and tissues. This aspect should be adequately considered when determining the SAR of MNP for magnetic hyperthermia

Transarterial chemoembolization with drug-eluting beads in patients with hepatocellular carcinoma: response analysis with mRECIST

PURPOSEAccording to the Barcelona Clinic Liver Cancer (BCLC) staging classification, transarterial chemoembolization (TACE) is the treatment of choice for intermediate hepatocellular carcinoma (HCC). Thereby, the use of drug-eluting beads (DEB) as embolic agents has been recently established in clinical practice. The aim of this study was to evaluate tumor response after DEB-TACE.METHODSThis retrospective study was approved by the institutional ethics committee. Overall, 89 patients with HCC (Child Pugh A or B) receiving DEB-TACE as palliative treatment option or as bridging before liver transplantation were included in the study. Tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST) and a tumor growth rate. Survival analysis was performed using Kaplan-Meier estimator with log-rank testing and Cox proportional hazards.RESULTSA total of 188 TACE procedures were performed between 2006 and 2010. After the last intervention, 18% achieved complete response, 45% achieved partial response, 28% had stable disease and 9% had progressive disease. Using the tumor growth rate, 90% of all patients showed a tumor reduction between first and final response evaluation. The 6-month, 1-, 2- and 3-year overall survival rates were 86.5%, 67.4%, 47.2%, and 33.7%, with a median survival of 45, 24, 15, and 14 months for complete response, partial response, stable disease, and progressive disease, respectively. Tumor reduction showed a positive effect on survival.CONCLUSIONDEB-TACE offers conclusive response results with mRECIST and proves a strong tendency of tumor reduction on survival benefits. Therefore, tumor growth rate represents a possible parameter to predict survival

Reliability of a risk-factor questionnaire for osteoporosis: a primary care survey study with dual energy x-ray absorptiometry ground truth

(1) Purpose: Predisposing factors to osteoporosis (OP) as well as dual-source x-ray densitometry (DXA) steer therapeutic decisions by determining the FRAX index. This study examines the reliability of a standard risk factor questionnaire in OP-screening. (2) Methods: n = 553 eligible questionnaires encompassed 24 OP-predisposing factors. Reliability was assessed using DXA as a gold standard. Multiple logistic regression and Spearman’s correlations, as well as the confounding influence of age and body mass index, were analyzed in SPSS (IBM Corporation, Armonk, NY, USA). (3) Results: Our study revealed low patient self-awareness regarding OP and its risk factors. One out of every four patients reported a positive history for osteoporosis not confirmed by DXA. The extraordinarily high incidence of rheumatoid arthritis and thyroid disorders likely reflect confusion with other diseases or health anxiety. FRAX-determining risk factors such as malnutrition, liver insufficiency, prior fracture without trauma, and glucocorticoid therapy did not correlate with increased OP incidence, altogether demonstrating how inaccurate survey information could influence therapeutic decisions on osteoporosis. (4) Conclusions: Contradictive results and a low level of patient self-awareness suggest a high degree of uncertainty and low reliability of the current OP risk factor survey

Systematic evaluation of particle loss during handling in the percutaneous transluminal angioplasty for eight different drug-coated balloons

Paclitaxel drug coated balloons (DCBs) should provide optimal drug transfer exclusively to the target tissue. The aim of this study was to evaluate the particle loss by handling during angioplasty. A robotic arm was developed for systematic and reproducible drug abrasion experiments. The contact force on eight different commercially available DCB types was gradually increased, and high-resolution microscopic images of the deflated and inflated balloons were recorded. Three types of DCBs were classified: no abrasion of the drug in both statuses (deflated and inflated), significant abrasion only in the inflated status, and significant abrasion in both statuses. Quantitative measurements via image processing confirmed the qualitative classification and showed changes of the drug area between 2.25 and 45.73% (13.28 ± 14.29%) in the deflated status, and between 1.66 and 40.41% (21.43 ± 16.48%) in the inflated status. The structures and compositions of the DCBs are different, some are significantly more susceptible to drug loss. Particle loss by handling during angioplasty leads to different paclitaxel doses in the target regions for same DCB types. Susceptibility to involuntary drug loss may cause side effects, such as varying effective paclitaxel doses, which may explain variations in studies regarding the therapeutic outcome

Diagnosing lung involvement in inflammatory rheumatic diseases—Where do we currently stand?

Lung involvement is the most common and serious organ manifestation in patients with inflammatory rheumatic disease (IRD). The type of pulmonary involvement can differ, but the most frequent is interstitial lung disease (ILD). The clinical manifestations of IRD-ILD and severity can vary from subclinical abnormality to dyspnea, respiratory failure, and death. Consequently, early detection is of significant importance. Pulmonary function test (PFT) including diffusing capacity of the lungs for carbon monoxide (DLCO), and forced vital capacity (FVC) as well as high-resolution computed tomography (HRCT) are the standard tools for screening and monitoring of ILD in IRD-patients. Especially, the diagnostic accuracy of HRCT is considered to be high. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) allow both morphological and functional assessment of the lungs. In addition, biomarkers (e.g., KL-6, CCL2 , or MUC5B) are being currently evaluated for the detection and prognostic assessment of ILD. Despite the accuracy of HRCT, invasive diagnostic methods such as bronchoalveolar lavage (BAL) and lung biopsy are still important in clinical practice. However, their therapeutic and prognostic relevance remains unclear. The aim of this review is to give an overview of the individual methods and to present their respective advantages and disadvantages in detecting and monitoring ILD in IRD-patients in the clinical routine

MRI-guided core needle biopsy of the prostate: acceptance and side effects

PURPOSEWe aimed to study side effects, complications, and patient acceptance of magnetic resonance imaging-guided real-time biopsy (MRI-GB) of the prostate.METHODSFifty-four men (49–78 years) with elevated prostate-specific antigen after at least one negative systematic transrectal ultrasound-guided biopsy (TRUS-GB) were included in a prospective clinical study. Suspicious areas on images were selectively sampled by obtaining a median of four specimens (range, 1–9 specimens) using MRI-GB. In TRUS-GB, a median of 10 specimens (range, 6–14 specimens) were obtained. Telephone interviews were conducted one week after outpatient MRI-GB, asking patients about pain and side effects (hematuria, hemospermia, rectal bleeding, fever, and chills) of the two biopsy procedures and which of the two procedures they preferred. Multinomial regression analysis and Fisher’s exact test was used to test for differences.RESULTSMRI-GB was preferred by 65% (35/54), and 82% (44/54) would undergo MRI-GB again. Pain intensity (P = 0.005) and bleeding duration (P = 0.004) were significantly lower for MRI-GB compared with TRUS-GB. Hematuria was less common after MRI-GB compared with TRUS-GB (P = 0.006). A high correlation was given between bleeding intensity and bleeding duration for TRUS-GB (r=0.77) and pain intensity and pain duration for MRI-GB (r=0.65). Although hemospermia, rectal hemorrhage, fever, and chills were less common in MRI, they showed no statistically significant difference.Z CONCLUSIONMRI-GB of the prostate seems to have fewer side effects and less pain intensity than TRUS-GB and was preferred by the majority of patients

Effect of matrix-modulating enzymes on the cellular uptake of magnetic nanoparticles and on magnetic hyperthermia treatment of pancreatic cancer models in vivo

Magnetic hyperthermia can cause localized thermal eradication of several solid cancers. However, a localized and homogenous deposition of high concentrations of magnetic nanomaterials into the tumor stroma and tumor cells is mostly required. Poorly responsive cancers such as the pancreatic adenocarcinomas are hallmarked by a rigid stroma and poor perfusion to therapeutics and nanomaterials. Hence, approaches that enhance the infiltration of magnetic nanofluids into the tumor stroma convey potentials to improve thermal tumor therapy. We studied the influence of the matrix-modulating enzymes hyaluronidase and collagenase on the uptake of magnetic nanoparticles by pancreatic cancer cells and 3D spheroids thereof, and the overall impact on magnetic heating and cell death. Furthermore, we validated the effect of hyaluronidase on magnetic hyperthermia treatment of heterotopic pancreatic cancer models in mice. Treatment of cultured cells with the enzymes caused higher uptake of magnetic nanoparticles (MNP) as compared to nontreated cells. For example, hyaluronidase caused a 28% increase in iron deposits per cell. Consequently, the thermal doses (cumulative equivalent minutes at 43 ◦C, CEM43) increased by 15–23% as compared to heat dose achieved for cells treated with magnetic hyperthermia without using enzymes. Likewise, heatinduced cell death increased. In in vivo studies, hyaluronidase-enhanced infiltration and distribution of the nanoparticles in the tumors resulted in moderate heating levels (CEM43 of 128 min as compared to 479 min) and a slower, but persistent decrease in tumor volumes over time after treatment, as compared to comparable treatment without hyaluronidase. The results indicate that hyaluronidase, in particular, improves the infiltration of magnetic nanoparticles into pancreatic cancer models, impacts their thermal treatment and cell depletion, and hence, will contribute immensely in the fight against pancreatic and many other adenocarcinomas