or more accurate dosimetric estimations relative to standard reference dosimetry. These data may help in optimizing imaging protocols and research studies, in particular when longer-lived isotopes are employed.Tau PET tracers exhibit varying levels of specific signal and distinct off-target binding patterns that are more diverse than amyloid PET tracers. This study compares two frequently used tau PET tracers, [18F]flortaucipir (FTP) and [18F]MK-6240, in the same subjects. METHODS [18F]flortaucipir and [18F]MK-6240 scans were collected within two months in 15 elderly subjects varying in terms of clinical diagnosis and cognition. FreeSurfer v5.3 was applied to 3T MR images to segment Braak pathologic regions (I-VI) for PET analyses. Off-target binding was assessed in choroid plexus, meninges, and striatum. SUVR outcomes were determined over 80-100 min ([18F]flortaucipir) or 70-90 min ([18F]MK-6240) normalized to cerebellar grey matter. Blinded visual interpretation of images was performed by five raters for both medial temporal lobe (MTL) and neocortex (NEO) and an overall (majority) rating determined. RESULTS Overall visual ratings showed complete concordance between radiotracers for both MTL and NEO.  https://www.selleckchem.com/products/msa-2.html  SUVR outcomes were highly correlated (r2>0.92; P less then less then 0.001) for all Braak regions except Braak II. The dynamic range of SUVR values in target regions was approximately two-fold higher for [18F]MK-6240 compared to [18F]flortaucipir. Cerebellar SUV values were similar for [18F]MK-6240 and [18F]flortaucipir, suggesting that differences in SUVR values are driven by specific signal. Apparent off-target binding in striatum and choroid plexus was often observed with [18F]flortaucipir, and most often in meninges with [18F]MK-6240. CONCLUSION Both [18F]MK-6240 and [18F]flortaucipir are capable of quantifying signal in a common set of brain regions that develop tau pathology in AD and perform equally well in visual interpretations. Each also shows distinct patterns of apparent off-target binding. [18F]MK-6240 showed greater dynamic range in SUVR estimates, which may be an advantage for detecting very early signal or in longitudinal studies designed to detect small interval changes.The poly-(adenosine diphosphate-ribose) polymerase (PARP) family of proteins participates in numerous functions, most notably the DNA damage response. Cancer vulnerability to DNA damage has led to development of several PARP inhibitors (PARPi). This class of drugs has demonstrated therapeutic efficacy in ovarian, breast, and prostate cancers, but with variable response. Consequently, clinics need to select patients likely to benefit from these targeted therapies. In vivo imaging of 18F-FluorThanatrace (18F-FTT) uptake has been shown to correspond to PARP-1 expression in tissue. This study characterizes the pharmacokinetics of 18F-FTT and tests kinetic and static models to guide metric selection in future studies assessing 18F-FTT as a biomarker of response to PARPi therapy. Methods Fourteen prospectively enrolled ovarian cancer patients were injected with 18F-FTT and imaged dynamically for 60-minutes post-injection followed by up to two whole-body scans, with venous blood activity and metabolite measurements. deviation, r≥0.79, p less then 0.05). Conclusion Tumor SUVmax and SUVpeak at 55-60 minutes post-injection and later and DVR from ≥ 60-minutes appear to be robust non-invasive measures of PARP-1 binding. 18F-FTT uptake in ovarian cancer was best described by models of reversible binding. However, pharmacokinetic patterns of tracer uptake were somewhat variable, especially at later time points.We sought to evaluate the performance of 68Ga-DOTA-FAPI-04 (68Ga-FAPI) PET/MR for the diagnosis of primary tumor and metastatic lesions in patients with gastric carcinomas and to compare the results with those of 18F-FDG PET/CT. Methods Twenty patients with histologically proven gastric carcinomas were recruited, and each patient underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/MR. A visual scoring system was established to compare the detectability of primary tumors and metastases in different organs/regions (the peritoneum, abdominal lymph nodes, supradiaphragmatic lymph nodes, liver, ovary, bone, and other tissues). The original maximum standardized uptake value (SUVmax) and normalized SUVmax (calculated by dividing a lesion's original SUVmax with the mean SUV of the descending aorta) of selected lesions on both 18F-FDG PET/CT and 68Ga-FAPI PET/MR were measured. Original/normalized SUVmax-FAPI and SUVmax-FDG were compared for patient-based (including a single lesion with the highest activity uptake in each ht be a promising method with the potential of replacing 18F-FDG PET/CT.Thiamine pyrophosphate (TPP) riboswitches regulate thiamine metabolism by inhibiting the translation of enzymes essential to thiamine synthesis pathways upon binding to thiamine pyrophosphate in cells across all domains of life. Recent work on the Arabidopsis thaliana TPP riboswitch suggests a multi-step TPP binding process involving multiple riboswitch configurational ensembles and that Mg2+ dependence underlies the mechanism of TPP recognition and subsequent transition to the expression-inhibiting state of the aptamer domain followed by changes in the expression platform. However, details of the relationship between TPP riboswitch conformational changes and interactions with TPP and Mg2+ ¬¬in the aptamer domain constituting this mechanism are unknown. Therefore, we integrated single-molecule multiparameter fluorescence and force spectroscopy with atomistic molecular dynamics simulations and found that conformational transitions within the aptamer domain's sensor helices associated with TPP and Mg2+ ligand binding occurred between at least five different ensembles on timescales ranging from µs to ms. These dynamics are orders of magnitude faster than the 10 second-timescale folding kinetics associated with expression-state switching in the switch sequence. Together, our results show that a TPP and Mg2+ dependent mechanism determines dynamic configurational state ensemble switching of the aptamer domain's sensor helices that regulates the stability of the switch helix, which ultimately may lead to the expression-inhibiting state of the riboswitch. Additionally, we propose that two pathways exist for ligand recognition and that this mechanism underlies a kinetic rheostat-like behavior of the Arabidopsis thaliana TPP riboswitch.