Multimodal imaging‐guided photothermal therapy (PTT), for the therapy of cancer, based on a ferritin (FRT) nanocage loaded with the near‐infrared dye IR820 (designated DFRT) is demonstrated. The dual ...roles of DFRT (in imaging and PTT) are successfully balanced by using two different excitation wavelengths: 550 nm for high quantum‐yield fluorescence imaging on the one hand and 808 nm for photoacoustic imaging and PTT with high photothermal conversion efficiency on the other.
Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's ...disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT‐specific positron emission tomography radiotracer, ((−)‐(1‐(‐8‐(2‐fluoroethoxy)‐3‐hydroxy‐1,2,3,4‐tetrahydronaphthalen‐2‐yl)piperidin‐4‐yl)(4‐fluorophenyl)‐methanone) (18FVAT) in macaques. Total volume distribution (VT) estimates were compared for one‐tissue compartment model (1TCM), two‐tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum‐hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for 18FVAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that 18FVAT has good reproducibility and reliability (TRV < 10%, ICC > 0.72). These studies demonstrate 18FVAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects.
PET imaging of vesicular acetylcholine transporter (VAChT) in brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease (AD). In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT‐specific PET radiotracer 18FVAT in macaques. The results demonstrated that 18FVAT is a promising VAChT PET tracer for quantitative assessment of VAChT levels in the brain of living subjects.
Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer ...molecule, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor®), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with (64)Cu. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment.
This Special Issue published one editorial, eight articles and four reviews from approximately one hundred authors. It aimed to provide cutting-edge research on pre-clinical development and the ...clinical translation of radiopharmaceuticals within the molecular imaging community. The Special Issue covered radioligand development, existing radiotracer optimization, imaging agent evaluation in animal models, the clinical production of radiopharmaceuticals, and investigative research on the use of molecular imaging probes in human subjects. We appreciate all the authors’ significant contributions to this Special Issue and hope the readers will enjoy the content.
Genome‐wide association studies have confirmed that schizophrenia is an inheritable multiple‐gene mental disorder. Longitudinal studies about depression, first episode psychosis (FEP) and acute ...psychotic relapse have mostly searched for brain imaging biomarkers and inflammatory markers from the blood. However, to the best of our knowledge, the association between enzymatic activities with diagnosis or prediction of treatment response in people with schizophrenia has barely been validated. Under the Longitudinal Study of National Mental Health Work Plan (2015‐2020), we have studied a subsample of approximately 36 individuals from the cohort with data on palmitoyl‐protein thioesterase‐1 enzymatic activity from FEP and performed a bivariate correlation analysis with psychiatric assessment scores. After adjusting for sex, age, body mass index (BMI) and total serum protein, our data demonstrated that PPT1 enzymatic activity is significantly associated with schizophrenia and its Positive and Negative Syndrome Scale (PANSS) scores. This longitudinal study compared the PPT1 enzymatic activity in FEP schizophrenia patients and healthy volunteers, and the former exhibited a significant 1.5‐fold increase in PPT1 enzymatic levels (1.79 mmol/L/h/mL, and 1.18 mmol/L/h/mL; P < 0.05; 95% CI, 2.3‐2.9 and 1.4‐1.8). The higher PPT1 enzymatic levels in FEP schizophrenia patients were positively associated with larger PANSS scaling scores (r = 0.32, P = 0.0079 for positive scaling; r = 0.41, P = 0.0006 for negative scaling; r = 0.45, P = 0.0001 for general scaling; and r = 0.34, P = 0.0048 for PNASS‐S scaling). Higher enzymatic PPT1 in FEP schizophrenia patients is significantly associated with increased PANSS scaling values, indicating more serious rates of developing psychosis. Enzymatic activity of PPT1 may provide an important new view for schizophrenia disorders.
Abusive head trauma (AHT) is a serious traumatic brain injury and the leading cause of death in children younger than 2 years. The development of experimental animal models to simulate clinical AHT ...cases is challenging. Several animal models have been designed to mimic the pathophysiological and behavioral changes in pediatric AHT, ranging from lissencephalic rodents to gyrencephalic piglets, lambs, and non-human primates. These models can provide helpful information for AHT, but many studies utilizing them lack consistent and rigorous characterization of brain changes and have low reproducibility of the inflicted trauma. Clinical translatability of animal models is also limited due to significant structural differences between developing infant human brains and the brains of animals, and an insufficient ability to mimic the effects of long-term degenerative diseases and to model how secondary injuries impact the development of the brain in children. Nevertheless, animal models can provide clues on biochemical effectors that mediate secondary brain injury after AHT including neuroinflammation, excitotoxicity, reactive oxygen toxicity, axonal damage, and neuronal death. They also allow for investigation of the interdependency of injured neurons and analysis of the cell types involved in neuronal degeneration and malfunction. This review first focuses on the clinical challenges in diagnosing AHT and describes various biomarkers in clinical AHT cases. Then typical preclinical biomarkers such as microglia and astrocytes, reactive oxygen species, and activated
-methyl-D-aspartate receptors in AHT are described, and the value and limitations of animal models in preclinical drug discovery for AHT are discussed.
Background
Birth trauma accounts for 1–2% of the mortality in newborns with significant intracranial injuries presenting in the immediate postnatal period. However, a significant number of ...asymptomatic neonates harbor birth-related intracranial hemorrhage (ICH), with birth-related subdural hemorrhage (SDH) being a common occurrence on infant brain CT and MRI studies performed as a standard of care for a variety of reasons. Although clinically insignificant, birth-related SDH is frequently brought up in courts as an alternative explanation for SDH in suspected abusive head trauma.
Objective
The aim of this study was to determine prevalence, imaging morphology and distribution of birth-related SDHs on brain CT and MRI studies obtained as a standard of care in infants up to 1 month old. We further tried to ascertain the relationship of birth-related SDHs with mode of delivery and birth weight.
Materials and methods
Infants up to the age of 1 month who had CT or MRI of the brain performed between Jan. 1, 2018, and March 29, 2020, were included in this retrospective observational study. In addition to the imaging data, we reviewed clinical history, birth history including birth weight and mode of delivery, and final diagnoses.
Results
Two hundred six infants younger than 30 days (range 0–29 days, mean 11.9 days, median 11 days and standard deviation SD 8.4 days) had a CT or MRI study during the study period. Among these, 58 infants were excluded as per the exclusion criteria. Among the included 148 infants, 88 (59.5%) had no imaging evidence of SDH. An additional 56 (37.8%) infants were assessed as having birth-related SDH based on review of clinical data. Within the birth-related SDH cohort (56 infants), only supratentorial SDH was identified in 5 (8.9%), only infratentorial SDH was identified in 14 (25%), while SDHs within both compartments were identified in 37 (66.1%) infants. The most common location for supratentorial birth-related SDH was along the occipital lobes (31/42, 73.8%), with other common locations being along the posterior interhemispheric fissure (30/42, 71.4%) and fronto-parietal convexity (9/42, 21.4%). The distribution of posterior fossa SDH was along the tentorium (38/51, 74.5%), along the cerebellum (38/51, 74.5%) and in both the locations (25/51, 49.0%). The rate of SDH was significantly higher in vaginal delivery group (46/84, 54.7%) as compared to caesarean section group (10/57, 17.5%) (
P
<0.05). We did not find any statistically significant difference between the birth weights of normal and birth-related SDH cohorts (
P
>0.05).
Conclusion
Birth-related SDH is a common occurrence, with our study suggesting a prevalence of 37.8%. The most common distribution of birth-related SDH is within both the supra- and infratentorial compartments (66.1%) followed by infratentorial compartment (25%). The rate of birth-related SDH was significantly higher in vaginal delivery group as compared to caesarean section group.
Abusive head trauma (AHT) is a leading cause of mortality and morbidity in child abuse, with a mortality rate of approximately 25%. In survivors, the prognosis remains dismal, with high prevalence of ...cerebral palsy, epilepsy and neuropsychiatric disorders. Early and accurate diagnosis of AHT is challenging, both clinically and radiologically, with up to one-third of cases missed on initial examination. Moreover, most of the management in AHT is supportive, reflective of the lack of clear understanding of specific pathogenic mechanisms underlying secondary insult, with approaches targeted toward decreasing intracranial hypertension and reducing cerebral metabolism, cell death and excitotoxicity. Multiple studies have elucidated the role of pro- and anti-inflammatory cytokines and chemokines with upregulation/recruitment of microglia/macrophages, oligodendrocytes and astrocytes in severe traumatic brain injury (TBI). In addition, recent studies in animal models of AHT have demonstrated significant upregulation of microglia, with a potential role of inflammatory cascade contributing to secondary insult. Despite the histological and biochemical evidence, there is a significant dearth of specific imaging approaches to identify this neuroinflammation in AHT. The primary motivation for development of such imaging approaches stems from the need to therapeutically target neuroinflammation and establish its utility in monitoring and prognostication. In the present paper, we discuss the available data suggesting the potential role of neuroinflammation in AHT and role of radiotracer imaging in aiding diagnosis and patient management.
Purpose
Dysregulation of sphingosine 1-phosphate receptor 1 (S1PR1) signaling contributes to inflammation-related pathophysiological changes in cardiovascular diseases including atherosclerosis (AS). ...S1PR1-targeting compounds significantly reduce lesion size in murine models of AS. Therefore, characterization of S1PR1 expression
in vitro
and
in vivo
in atherosclerotic plaque could enable mechanistic studies and inform S1PR1 targeted therapies.
Procedures
H&E staining and immunostaining studies were performed on variably diseased human femoral endarterectomy plaque specimens, as well as mouse aortic sections from ApoE
−/−
mice maintained on a high-fat diet (AS mice).
In vitro
autoradiography study in human femoral plaques was used to confirm the tracer specificity. Micro positron emission tomography (PET) and
ex vivo
autoradiography studies were conducted in AS mice and their controls using a S1PR1-specific radioligand
11
CTZ3321 for
in vivo
and
ex vivo
quantification of S1PR1 expression in mouse aortic plaques.
Results
Increased S1PR1 expression was observed in areas of human femoral endarterectomy plaque specimens with foam cell accumulation compared with control tissue;
in vitro
autoradiography study indicated that SEW2781, a S1PR1 compound was able to reduce the uptake of
11
CTZ3321 by 56 %. S1PR1 levels were also upregulated in AS mouse aortic plaques. MicroPET data showed the aorta-to-blood tracer uptake ratio in AS mice was approximately 20 % higher than that in controls. Autoradiographic study also revealed elevated tracer accumulation in AS mouse aorta
.
Conclusions
Upregulated S1PR1 expression in human and mouse atherosclerotic plaques was successfully identified by immunostaining and radioligand-based methods. This data demonstrates that
11
CTZ3321 PET provides great promise in imaging S1PR1 expression in atherosclerotic plaques.
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