The prostate cancer molecular imaging standardized evaluation (PROMISE) V2 framework enables standardized reporting of disease extent using prostate-specific membrane antigen (PSMA) targeting ...positron emission tomography for prostate cancer. PSMA-expression assessment of lesions and a framework for longitudinal assessment of metastatic disease were integrated. PROMISE V2 improves communication between imaging experts and referring physicians.
Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) is emerging to become a reference imaging tool for the staging and restaging of patients with prostate cancer for both clinical routine and trials. The prostate cancer molecular imaging standardized evaluation (PROMISE) criteria have been proposed as a framework for whole-body staging (molecular imaging TNM staging, denoted miTNM staging) to describe the prostate cancer disease extent on PSMA-PET.
To create a comprehensive and integrated framework for PSMA-PET image interpretation and reporting.
We propose the PROMISE V2 framework, which integrates an updated miTNM system, improved assessment of local disease, and a slightly modified PSMA-expression score for clinical routine. We have added a response monitoring framework defining qualitative and quantitative parameters to be recorded for a longitudinal assessment in clinical trials.
We provide a comprehensive literature review on the current use of the PROMISE framework in clinical research and prospective trials. PROMISE variables demonstrate a clear association with survival. PSMA expression assessed by the PSMA-expression score was used in several trials, and a low PSMA-expression score is a negative prognosticator of overall survival after 177Lu-PSMA radioligand therapy. The proposed imaging parameters recorded for response assessment in clinical trials can be utilized to determine response according to PSMA-PET progression (PPP) or Response Evaluation Criteria in PSMA-PET/Computed Tomography (RECIP) frameworks, but also future response criteria.
PROMISE V2 offers standardized reporting of disease extent for clinical routine and research. Parameters recorded within clinical trials facilitate objective response assessment.
Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) has become a standard imaging examination for prostate cancer. We propose a comprehensive framework for the analysis and reporting of PSMA-PET findings that will improve the communication between imaging experts and uro-oncologists.
Increasing the service-life of engineering structures such as aeroplanes is a major issue in order to enhance their cost-effectiveness and to reduce the carbon footprint. One possibility to achieve ...this goal is to determine the current structural health state and to derive respective measures in order to increase the structure’s technical reliability. For doing so, a structural health monitoring system consisting of both an actuator and a sensor network may be applied. Whereas the actuator induces a wave field of guided ultrasonic waves, the measuring data of the sensors allows to determine the health state of the respective structure. However, both actuators and sensors in most cases distort these wave fields. This distortion may lead to false-detection of damage: both the number and severity of damage may be over- or underestimated. The former leads to an unnecessary high effort for retrofitting the structure, whereas the latter reduces the structure’s technical reliability. Several measures exist in order to avoid such false-detections. In the present contribution, focus is set on reducing the distortion of the wave field which is caused by an embedded sensor. The reduced distortion of the wave field is achieved by an acoustic impedance matching with a functionally graded material which is based on a mechanical model. The approach additionally results in amplified measuring signals of the sensor. The applicability of the proposed approach is shown by means of a numerical study.
The main purpose of this study was to assess the reliability of shape and heterogeneity features in both the PET and the low-dose CT components of PET/CT. A secondary objective was to investigate the ...impact of image quantization.
A Health Insurance Portability and Accountability Act-compliant secondary analysis of deidentified prospectively acquired PET/CT test-retest datasets of 74 patients from multicenter Merck and American College of Radiology Imaging Network trials was performed. Metabolically active volumes were automatically delineated on PET with a fuzzy locally adaptive bayesian algorithm. Software was used to semiautomatically delineate the anatomic volumes on the low-dose CT component. Two quantization methods were considered: a quantization into a set number of bins (quantization B) and an alternative quantization with bins of fixed width (quantization W). Four shape descriptors, 10 first-order metrics, and 26 textural features were evaluated. Bland-Altman analysis was used to quantify repeatability. Features were subsequently categorized as very reliable, reliable, moderately reliable, or poorly reliable with respect to the corresponding volume variability.
Repeatability was highly variable among features. Numerous metrics were identified as poorly or moderately reliable. Others were reliable or very reliable in both modalities and in all categories (shape and first-, second-, and third-order metrics). Image quantization played a major role in feature repeatability. Features were more reliable in PET with quantization B, whereas quantization W showed better results in CT.
The test-retest repeatability of shape and heterogeneity features in PET and low-dose CT varied greatly among metrics. The level of repeatability also depended strongly on the quantization step, with different optimal choices for each modality. The repeatability of PET and low-dose CT features should be carefully considered when selecting metrics to build multiparametric models.
Targeted delivery represents a promising approach for the development of safer and more effective therapeutics for oncology applications. Although macromolecules accumulate nonspecifically in tumors ...through the enhanced permeability and retention (EPR) effect, previous studies using nanoparticles to deliver chemotherapeutics or siRNA demonstrated that attachment of cell-specific targeting ligands to the surface of nanoparticles leads to enhanced potency relative to nontargeted formulations. Here, we use positron emission tomography (PET) and bioluminescent imaging to quantify the in vivo biodistribution and function of nanoparticles formed with cyclodextrin-containing polycations and siRNA. Conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to the 5' end of the siRNA molecules allows labeling with ⁶⁴Cu for PET imaging. Bioluminescent imaging of mice bearing luciferase-expressing Neuro2A s.c. tumors before and after PET imaging enables correlation of functional efficacy with biodistribution data. Although both nontargeted and transferrin-targeted siRNA nanoparticles exhibit similar biodistribution and tumor localization by PET, transferrin-targeted siRNA nanoparticles reduce tumor luciferase activity by almost equal to50% relative to nontargeted siRNA nanoparticles 1 d after injection. Compartmental modeling is used to show that the primary advantage of targeted nanoparticles is associated with processes involved in cellular uptake in tumor cells rather than overall tumor localization. Optimization of internalization may therefore be key for the development of effective nanoparticle-based targeted therapeutics.
Glucose and glutamine are the two principal nutrients that cancer cells use to proliferate and survive. Many cancers show altered glucose metabolism, which constitutes the basis for in vivo positron ...emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)F-FDG). However, (18)F-FDG is ineffective in evaluating gliomas because of high background uptake in the brain. Glutamine metabolism is also altered in many cancers, and we demonstrate that PET imaging in vivo with the glutamine analog 4-(18)F-(2S,4R)-fluoroglutamine ((18)F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced (18)F-FGln tumor avidity, corresponding with decreased tumor burden. (18)F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where (18)F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that (18)F-FGln is avidly taken up by gliomas, can be used to assess metabolic nutrient uptake in gliomas in vivo, and may serve as a valuable tool in the clinical management of gliomas.
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this ...cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition over time to calculate effective doses for individual drugs. Using patient-derived xenografts, we demonstrate that different therapeutics achieve similar integrated inhibition efficiencies under different dosing regimens. This imaging approach to non-invasive, quantitative assessment of dynamic intratumoral target inhibition may improve patient care through real-time monitoring of drug delivery.
In organizational psychology the positive effects of democratically structured enterprises on their employees are well documented. However, the longstanding viability as well as economic success of ...democratic enterprises in a capitalistic market environment has long been contested. For instance, this has given rise to widespread endorsement of the “degeneration thesis” and the so-called “iron law of oligarchy”. By reviewing 77 qualitative studies that examined 83 democratic enterprises (including 15 studies on nine enterprises of the Mondragon Cooperative Cooperation network) within the last 50 years, the present systematic review provides evidence that such enterprises are able to economically survive and prosper. The majority of studied enterprises (63.5%) either resisted pressures toward degeneration or subsequently regenerated after undergoing degenerative processes. Only 9.5% fully degenerated in accordance with the degeneration thesis and the “iron law of oligarchy”, while 27.0% of the democratic enterprises showed diverse and mixed forms of degeneration tendencies, indicating that the notion of an “iron law” needs to be revised. Within the nine investigated cases of Mondragon not one single enterprise or group fully degenerated. Three cases showed degenerative tendencies, another three one degeneration tendencies and simultaneously regeneration, one case fully resisted degeneration tendencies (retention) and two cases regenerated. Further, this systematic review provides an overview of organizational and external conditions, non-/democratic or non-/participative practices and psychological phenomena that contribute to the degeneration, regeneration, or resistance to degeneration (i.e., retention). The described examples of such practices may help practitioners to implement and maintain democratic structures and processes in contemporary organizations.
PDF
