UNASSIGNED: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs.
UNASSIGNED: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy.
UNASSIGNED: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.

Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age.
To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration.
Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information.
One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing.
No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Epac1-/- mice, but not Epac2-/- mice have elevated baseline permeability to albumin. This study extends the investigations of how Epac-dependent pathways modulate transvascular exchange in response to the classical inflammatory agent histamine. It also evaluates the limitations of models of blood-to-tissue exchange in transgenic mice in DCE-MRI measurements.
We measured DCE-MRI signal intensity in masseter muscle of wt and Epac1-/- mice with established approaches from capillary physiology to determine how changes in blood flow and vascular permeability contribute to overall changes of microvascular flux. We used two tracers, the high molecular weight tracer (Gadomer-17, MW 17 kDa, apparent MW 30-35 kDa) is expected to be primarily limited by diffusion and therefore less dependent on changes in blood flow and the low molecular weight tracer (Dotarem (MW 0.56 kDa) whose transvascular exchange is determined by both blood flow and permeability. Paired experiments in each animal combined with analytical methods provided an internally consistent description of microvascular transport.
Epac1-/- mice had elevated baseline permeability relative to wt control mice for Dotarem and Gadomer-17. In contrast to wt mice, Epac1-/- mice failed to increase transvascular permeability in response to histamine. Dotarem underestimated blood flow and vascular volume and Gadomer-17 has limited sensitivity in extravascular accumulation.
The study suggests that the normal barrier loosening effect of histamine in venular microvessels do not function when the normal barrier tightening effect of Epac1 is already compromised. The study also demonstrated that the numerical analysis of DCE-MRI data with tracers of different molecular weight has significant limitations.