Meadowsfields7698

FERM stability is demonstrated by a high correlation between 19F and 89Zr content in blood (correlation coefficient > 0.99). Image sensitivity is observed in an acute infection rodent model at low dose (37 kBq). The versatility of FERM is further demonstrated in inflammatory bowel disease and 4T1 tumor models. Conclusion Multimodal detection using FERM yields robust whole-body lesion detection and leverages the strengths of combined PET/19F MRI. FERM nanoemulsion production is scalable and potentially useful for precise diagnosis, stratification and treatment monitoring of inflammatory diseases.Introduction Tc-99m-labeled Mas3-y-nal-k(Sub-KuE) (Tc-99m-PSMA I&S) is a prostate specific membrane antigen (PSMA) tracer that can be used for planar and SPECT/CT gamma imaging and radio-guided surgery (RGS). The primary aim of this study was to estimate the dosimetry of Tc-99m-PSMA I&S using a hybrid method (sequential gamma planar imaging and one single SPECT/CT) in healthy volunteers. The secondary aim was to depict the tracer biodistribution and tumor-to-background ratios (TBR) in patients with prostate cancer (PCa). Methods Dosimetry of Tc-99m-PSMA I&S was investigated in four healthy volunteers. Whole-body planar imaging was acquired at 1, 2, 3, 6 and 24 hours, and SPECT/CT at 6h after tracer injection. Contours of organs were drawn on all acquisitions to determine organ activity at each timepoint. Absorbed dose was estimated using two Methods 1) independent curve-fitting manual method (Levenberg-Marquardt-based algorithm using dose factors from Radiation Dose Assessment Resource (RADAR) web site) and 2-PSMA I&S SPECT/CT showed high TBR in PCa patients. This study can provide required data for translation and approval of Tc-99m-PSMA I&S by regulatory agencies.For over 40 years, 18F-FDG has been the dominant PET tracer in neurology, cardiology, inflammatory diseases, and, most particularly, oncology. Combined with the ability to perform whole-body scanning, 18F-FDG has revolutionized the evaluation of cancer and has stifled the adoption of other tracers, except in situations where low avidity or high background activity limits diagnostic performance. The strength of 18F-FDG has generally been its ability to detect disease in the absence of structural abnormality, thereby enhancing diagnostic sensitivity, but its simultaneous weakness has been a lack of specificity due to diverse pathologies with enhanced glycolysis. Radiotracers that leverage other hallmarks of cancer or specific cell-surface targets are gradually finding a niche in the diagnostic armamentarium. However, none have had sufficient sensitivity to realistically compete with 18F-FDG for evaluation of the broad spectrum of malignancies. Perhaps, this situation is about to change with development of a class of tracers targeting fibroblast activation protein that have low uptake in almost all normal tissues but high uptake in most cancer types. In this review, the development and exciting preliminary clinical data relating to various fibroblast activation protein-specific small-molecule inhibitor tracers in oncology will be discussed along with potential nononcologic applications.In 2018, the National Cancer Institute (NCI) and the NRG Oncology partnered for the first time to host a joint Workshop on Systemic Radiopharmaceutical Therapy (RPT) to specifically address issues and strategies of dosimetry for future clinical trials. The workshop focused on (1) current dosimetric approaches for clinical trials, (2) strategies under development that would provide optimal dose reporting, and (3) future desired/optimized approaches for the new and novel emerging radionuclides and carriers in development. In this proceedings, we review the main approaches that are applied clinically to calculate the absorbed dose These include absorbed doses calculated over a variety of spatial scales including organ, suborgan, and voxel, all achievable within the Medical Internal Radiation Dose (MIRD) schema (S-value) can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This proceeding will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biological effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We will also discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation-when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Almost all these drugs, which in general have a long residence time in the body, can stably be labeled with 89Zr for whole-body PET imaging and quantification. TP-0903 datasheet Although not restricted to monoclonal antibodies, this approach is called 89Zr-immuno-PET. This review summarizes the state of the art of the technical aspects of 89Zr-immuno-PET and illustrates why it has potential for steering the design, development, and application of biologic drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biologic drug formats and disease targets. In addition, an overview of ongoing and completed clinical trials is provided. Although 89Zr-immuno-PET is a young tool in drug development, its application is rapidly expanding, with first clinical experiences giving insight on why certain drug-target combinations might have better perspectives than others.Purpose Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of prostate cancer theranostic agents. 18F-rhPSMA-7, offers the advantages of 18F-labelling and low urinary excretion compared with 68Ga-PSMA-11. Here, we compare frequency of non-tumor related uptake and tumor positivity with 68Ga-PSMA-11 and 18F-rhPSMA-7 in patients with primary or recurrent prostate cancer. Methods This retrospective matched-pair comparison matched 160 18F-rhPSMA-7 with 160 68Ga-PSMA-11 PET/CT studies for primary staging (n = 33) and biochemical recurrence (n = 127) according to clinical characteristics. Two nuclear medicine physicians reviewed all scans, first, identifying all PET-positive lesions, then differentiating lesions suspicious for prostate cancer from those that were benign, based on known pitfalls and ancillary information from CT. For each region, SUVmax of the lesion with the highest PSMA-ligand uptake was noted. Tumor positivity rates were determined and SUVmax were compared separately f 18F-rhPSMA-7. Both tracers revealed a considerable number of areas of uptake that were reliably identified as benign by trained physicians making use of corresponding morphological imaging and known PSMA pitfalls. These were more frequent with 18F-rhPSMA-7. However, the matched-pair comparison could have introduced a source of bias. Adequate reader training can allow physicians to differentiate benign uptake from disease and be able to benefit from the logistical and clinical advantages of 18F-rhPSMA-7.Purpose Prostate-specific membrane antigen targeted radioligand therapy (PSMA-RLT) is effective against prostate cancer (PCa), but all patients relapse eventually. Poor understanding of the underlying resistance mechanisms represents a key barrier to development of more effective RLT. We investigate the proteome and phosphoproteome in a mouse model of PCa to identify signaling adaptations triggered by PSMA-RLT. Experimental Design Therapeutic efficacy of PSMA-RLT was assessed by tumor volume measurements, time to progression, and survival in C4-2 or C4-2 TP53-knockout tumor-bearing Nod scid gamma mice. link2 Two days post-RLT, the (phospho)proteome was analyzed by mass spectrometry. PSMA-RLT significantly improved disease control in a dose-dependent manner. (Phospho)proteomic datasets revealed activation of genotoxic stress response pathways, including deregulation of DNA damage/replication stress response, TP53, androgen receptor, PI3K/AKT, and MYC signaling. C4-2 TP53-knockout tumors were less sensitive to PSMA-RLT than parental counterparts, supporting a role for TP53 in mediating RLT responsiveness. Conclusion We identified signaling alterations that may mediate resistance to PSMA-RLT in a PCa mouse model. Our data enable the development of rational synergistic RLT-combination therapies to improve outcomes for PCa patients.The PET radiotracer [18F]-(2S,4R)4¬-Fluoroglutamine (18F-Gln) reflects glutamine transport and can be used to infer glutamine metabolism. link3 Mouse xenograft studies have demonstrated that 18F-Gln uptake correlates directly with glutamine pool size and is inversely related to glutamine metabolism through the glutaminase enzyme. To provide a framework for the analysis of 18F-Gln-PET, we have examined 18F-Gln uptake kinetics in mouse models of breast cancer at baseline and after inhibition of glutaminase. We describe results of the pre-clinical analysis and computer simulations with the goal of model validation and performance assessment in anticipation of human breast cancer patient studies. Methods TNBC and receptor-positive xenografts were implanted in athymic mice. PET mouse imaging was performed at baseline and after treatment with a glutaminase inhibitor (CB-839, Calithera, Inc.) or a vehicle solution for a total of four mouse groups. Dynamic PET images were obtained for one hour beginning at the time of intr and Logan analyses. Conclusion Kinetic analysis of dynamic 18F-Gln-PET images demonstrated the ability to measure VD to estimate glutamine pool size, a key indicator of cellular glutamine metabolism, by both a one-compartment model and Logan analysis. Changes in VD with glutaminase inhibition supports the ability to assess response to glutamine metabolism-targeted therapy. Concordance of kinetic measures with tumor-to-blood ratios provides a clinically feasible approach for human imaging.The COVID-19 pandemic has affected more than 20 million people worldwide, with mortality exceeding 800,000 patients. Risk factors associated with severe disease and mortality include advanced age, hypertension, diabetes, and obesity. Each of these risk factors pathologically disrupts the lipidome, including immunomodulatory eicosanoid and docosanoid lipid mediators (LMs). We hypothesized that dysregulation of LMs may be a defining feature of the severity of COVID-19. By examining LMs and polyunsaturated fatty acid precursor lipids in serum from hospitalized COVID-19 patients, we demonstrate that moderate and severe disease are separated by specific differences in abundance of immune-regulatory and proinflammatory LMs. This difference in LM balance corresponded with decreased LM products of ALOX12 and COX2 and an increase LMs products of ALOX5 and cytochrome p450. Given the important immune-regulatory role of LMs, these data provide mechanistic insight into an immuno-lipidomic imbalance in severe COVID-19.