Multicentric 68Ga-PSMA PET radiomics for treatment response assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

ObjectiveThe treatment with 177Lutetium PSMA (177Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by the FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomic parameters extracted from pretreatment 68Ga-PSMA PET images for the prediction of treatment response.MethodsA total of 45 mCRPC patients treated with 177Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomic features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomic features and combinations thereof. Further, overall survival was predicted by using the identified radiomic signature and compared to a Cox regression model based on age and PET parameters.ResultsThe machine learning model based on a combined radiomic signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross-validation and outperformed models based on age and PET parameters or radiomic features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomic signature showed the best performance to predict overall survival (C-index, 0.67).ConclusionOur results demonstrate that a machine learning model to predict response to 177Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomic signature based on pretreatment 68Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making

Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts

68Ga-PSMA PET/CT for monitoring response to 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

Purpose To evaluate the use of Ga-68-PSMA PET/CT for monitoring response to Lu-177-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with Lu-177-PSMA-617 and whose records included Ga-68-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle. A treatment response based on Ga-68-PSMA PET/CT was defined according to a modified version of the PERCIST criteria. A decline in PSA level of >= 50% was considered the reference standard. The sensitivity, specificity, positive and negative predictive values, and ROC curves were calculated, and patient survival times in relation to the PET results were also analysed. Results Ga-68-PSMA PET/CT had a sensitivity of about 85% and a specificity of between 55% and 65%. The negative and positive predictive values ranged between 70% and 78%. The fitted ROC area was 0.70. The survival time was about 19.6 months in patients with a treatment response, while nonresponders had a survival time of about 15.9 months. However, this difference between the groups was not statistically significant. Conclusion Our results indicate that Ga-68-PSMA PET/CT could be a useful tool for the evaluation of response to Lu-177-PSMA-617 radioligand therapy within a theranostic framework

Incidences of Mould and Bacterial Toxins in Dairy Products

This chapter reviews the common bacterial toxins and mycotoxins involved in food poisoning in milk and dairy products. Food-borne bacterial infection occurs when food contaminated with pathogenic bacteria is consumed. The major type of diseases caused by B. cereus varies from countries to countries. Although the incidence of these bacteria has frequently been reported in different food-stuffs including dairy products, there is no information about the occurrence and analysis of their toxins produced in food. Contamination of dried milk products with B. cereus is common, and generally via raw milk that contains the organisms. Milk and dairy products are known to be frequently contaminated with B. cereus (emetic), C. botulinum and Staph. aureus. Botulinum neurotoxin (BoNT) causes the disease botulism, which can be lethal if untreated. Rapid determination of exposure to BoNT is an important public health goal