Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical ...management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions.
Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 (
Zr
). The targeting potential of this probe was compared with unspecific
Zr-HSA and
F-FDG in an experimental model of atherosclerosis (
mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls.
PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of
Zr-Mal-HSA in the atherosclerotic lesions of
mice. The maximum standardized uptake values (SUV
) for
Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (
<0.05) in
mice than in control WT mice, whereas no difference in SUV
was observed for
F-FDG in the same animals.
Zr-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (
<0.01) for
mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (
<0.001) for
Zr-Mal-HSA compared with unspecific
Zr-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of
Zr-Mal-HSA in the aortas of
mice than in WT mice (9.4±1.4 vs 0.8±0.3%;
<0.001).
Zr radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of
mice, as demonstrated by quantitative in vivo PET/MRI.
Zr-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.
In this paper we analyze and classify the dynamics of SIQRS epidemiological models with susceptible, infected, quarantined, and recovered classes, where the recovered individuals can become ...reinfected. We are able to treat general incidence functional responses. Our models are more realistic than what has been studied in the literature since they include two important types of random fluctuations. The first type is due to small fluctuations of the various model parameters and leads to white noise terms. The second type of noise is due to significant environment regime shifts in the that can happen at random. The environment switches randomly between a finite number of environmental states, each with a possibly different disease dynamic. We prove that the long-term fate of the disease is fully determined by a real-valued threshold \(\lambda\). When \(\lambda < 0\) the disease goes extinct asymptotically at an exponential rate. On the other hand, if \(\lambda > 0\) the disease will persist indefinitely. We end our analysis by looking at some important examples where \(\lambda\) can be computed explicitly, and by showcasing some simulation results that shed light on real-world situations.
•Chiral column chromatography (CCC) is a crucial methodology in assistance of radiopharmaceutical and drug development approaches.•The last three-decade advances and application of CCC in ...enantioresolution of positron emission tomography tracers are reviewed.•The effective parameters in CCC performance are addressed.•Application and potential of chiral supercritical fluid chromatography in radiopharmaceutical was discussed.•The challenges and upcoming prospects in CCC field are discussed.
Chiral column chromatography (CCC) is a revolutionary analytical methodology for the enantioseparation of novel positron emission tomography (PET) tracers in the primary stages of drug development. Due to the different behaviors of tracer enantiomers (e.g. toxicity, metabolism and side effects) in administrated subjects, their separation and purification is a challenging endeavor. Over the last three decades, different commercial chiral columns have been applied for the enantioseparation of PET-radioligand (PET-RL) or radiotracers (PET-RT), using high-performance liquid chromatography (HPLC). The categorization and reviewing of them is a vital topic. This review presents a brief overview of advances, applications, and future prospectives of CCC in radiopharmaceutical approaches. In addition, the effective chromatographic parameters and degravitation trends to enhance enantioseparation resolution are addressed. Moreover, the application and potential of chiral super fluidical chromatography (CSFC) as an alternative for enantioseparation in the field of radiopharmaceutical is discussed. Finally, the crucial application challenges of CCC are explained and imminent tasks are suggested.
In this paper we focus on the convergence analysis of the forward-backward splitting method for solving nonsmooth optimization problems in Hilbert spaces when the objective function is the sum of two ...convex functions. Assuming that one of the functions is Fréchet differentiable and using two new linesearches, the weak convergence is established without any Lipschitz continuity assumption on the gradient. Furthermore, we obtain many complexity results of cost values at the iterates when the stepsizes are bounded below by a positive constant.
Correct and timely diagnosis of pancreatic cancer (PC) is essential for treatment selection but is still clinically challenging. Standard-of-care imaging methods can sometimes not differentiate ...malignancies from inflammatory lesions or detect malignant transformation in premalignant lesions. This interim analysis of a prospective clinical trial aimed to evaluate the diagnostic accuracy of
Gafibroblast activation protein inhibitor (FAPI)-46 PET/CT for PC and determine the sample size needed to demonstrate whether this imaging technique improves the characterization of equivocal lesions detected by standard-of-care imaging methods.
GaFAPI-46 PET/CT imaging was performed on 30 patients scheduled for surgical resection of suspected PC. Target lesions were delineated, SUV
and SUV
were determined, and the results were compared with those of standard-of-care imaging. Receiver operating characteristics were calculated for the whole cohort and a subcohort of 11 patients with an equivocal clinical imaging work-up preoperatively. Postoperative histopathologic findings served as a reference standard, and the statistical power was determined.
Histopathologic examination revealed malignancy in 20 patients and benign lesions in 10 patients. Significantly elevated
GaFAPI-46 uptake was observed in malignant tumors compared with benign lesions (
< 0.001). Receiver-operating-characteristic analyses established optimal cutoffs for both SUVs for differentiation of malignant from nonmalignant pancreatic tumors. The optimal SUV
cutoff was 10.2 and showed 95% sensitivity and 80% specificity for the whole cohort, as well as 100% diagnostic accuracy when considering the subcohort with equivocal imaging work-up only. For sufficient statistical power, 38 equivocal observations are needed.
We conclude that
GaFAPI-46 PET/CT can accurately differentiate malignant from benign pancreatic lesions deemed equivocal by standard-of-care imaging. This trial will therefore continue to recruit a total of 120 patients to reach those 38 equivocal observations needed for sufficient statistical power. On the basis of our findings, we propose that
GaFAPI-46 PET/CT not only can be clinically applied as a complement but also could become a necessary tool when standard-of-care imaging is inconclusive.
Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. ...Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with
GaGa-ABY-025 for visualization of HER2-low mBC.
A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with
GaGa-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of
GaGa-ABY-025. The SUV
was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events.
Ten patients with HER2-low mBC underwent
GaGa-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients,
GaGa-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV
and 1 in a liver metastasis with a high SUV
but a "cold" core.
The visualization of HER2-low mBC with
GaGa-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in
GaGa-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
To increase understanding of optimal imaging parameters 18 FPSMA-1007 when imaging patients with prostate cancer and to determine interrater agreement using 18 FPSMA-1007.
In this observational ...study, four independent physicians read reconstruction sets using bedtimes of 1, 2 and 3 minutes of patients undergoing 18 FPSMA-1007. positron emission topography. Clear and equivocal lesions and their locations were recorded. Image noise was rated on a four-point scale. Lesion counts were compared using inter-class correlation whereas noise ratings were compared using generalized estimating equations. Repeated cases were used to assess intra-rater agreement.
Sixty reconstruction sets of 16 consecutively examined participants were included. Participants had a mean age of 71.5 years, six of them were examined prior to any treatment, three had a history of radiotherapy and seven of prostatectomy. Median Gleason score of primary tumors was 7. Imaging was performed after a mean of 132 min using a mean 3.95 MBq/Kg body weight of 18 F PSMA-1007. Neither the total number of lesions per location nor the proportion of equivocal lesions varied consistently between bedtimes. Inter-rater reliability scores varied depending on location from 0.40 to 1.0 and were similar for all bedtimes. Intra-rater reliability varied between 0.70 and 0.76 for the three different bedtimes. Noise ratings were significantly lower for 1 minute than 3 minutes per bed.
In the setting of 18 FPSMA-1007 PET CT, 1, 2 and 3 minutes per bed produce similar results unlikely to affect clinical interpretation. Image noise ratings favor 2 and 3 minutes per bed.
We systematically study the optimal linear convergence rates for several relaxed alternating projection methods and the generalized Douglas-Rachford splitting methods for finding the projection on ...the intersection of two subspaces. Our analysis is based on a study on the linear convergence rates of the powers of matrices. We show that the optimal linear convergence rate of powers of matrices is attained if and only if all subdominant eigenvalues of the matrix are semisimple. For the convenience of computation, a nonlinear approach to the partially relaxed alternating projection method with at least the same optimal convergence rate is also provided. Numerical experiments validate our convergence analysis
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