[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

Purpose 111In (typically as [111In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an 89Zr PET tracer for cell labelling and compare it with [111In]oxinate3 single photon emission computed tomography (SPECT). Methods [89Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3 was monitored for up to 14 days. 89Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. Results Zr labelling was effective in all cell types with yields comparable with 111In labelling. Retention of 89Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with 111In or 89Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for 111In. In liver, spleen and bone marrow at least 92 % of 89Zr remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [89Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types

PET Cell Tracking Using 18F-FLT is Not Limited by Local Reuptake of Free Radiotracer

Assessing the retention of cell therapies following implantation is vital and often achieved by labelling cells with 2'-[(18)F]-fluoro-2'-deoxy-D-glucose ((18)F-FDG). However, this approach is limited by local retention of cell-effluxed radiotracer. Here, in a preclinical model of critical limb ischemia, we assessed a novel method of cell tracking using 3'-deoxy-3'-L-[(18)F]-fluorothymidine ((18)F-FLT); a clinically available radiotracer which we hypothesise will result in minimal local radiotracer reuptake and allow a more accurate estimation of cell retention. Human endothelial cells (HUVECs) were incubated with (18)F-FDG or (18)F-FLT and cell characteristics were evaluated. Dynamic positron emission tomography (PET) images were acquired post-injection of free (18)F-FDG/(18)F-FLT or (18)F-FDG/(18)F-FLT-labelled HUVECs, following the surgical induction of mouse hind-limb ischemia. In vitro, radiotracer incorporation and efflux was similar with no effect on cell viability, function or proliferation under optimised conditions (5 MBq/mL, 60 min). Injection of free radiotracer demonstrated a faster clearance of (18)F-FLT from the injection site vs. (18)F-FDG (p ≤ 0.001), indicating local cellular uptake. Using (18)F-FLT-labelling, estimation of HUVEC retention within the engraftment site 4 hr post-administration was 24.5 ± 3.2%. PET cell tracking using (18)F-FLT labelling is an improved approach vs. (18)F-FDG as it is not susceptible to local host cell reuptake, resulting in a more accurate estimation of cell retention

Advances in PET Detection of the Antitumor T Cell Response

Positron emission tomography (PET) is a powerful noninvasive imaging technique able to measure distinct biological processes in vivo by administration of a radiolabeled probe. Whole-body measurements track the probe accumulation providing a means to measure biological changes such as metabolism, cell location, or tumor burden. PET can also be applied to both preclinical and clinical studies providing three-dimensional information. For immunotherapies (in particular understanding T cell responses), PET can be utilized for spatial and longitudinal tracking of T lymphocytes. Although PET has been utilized clinically for over 30 years, the recent development of additional PET radiotracers have dramatically expanded the use of PET to detect endogenous or adoptively transferred T cells in vivo. Novel probes have identified changes in T cell quantity, location, and function. This has enabled investigators to track T cells outside of the circulation and in hematopoietic organs such as spleen, lymph nodes, and bone marrow, or within tumors. In this review, we cover advances in PET detection of the antitumor T cell response and areas of focus for future studies

Antioxidant and anti-inflammatory activities of durian (Durio zibethinus Murr.) pulp, seed and peel flour

The unripe pulp, inner peel and seed of durian were used in this study. These are generally not considered edible and must be disposed of as waste. However, they are good sources of bioactive compounds. Flour extracts from the unripe pulp, inner peel, and seed of two durian (Durio zibethinus Murr.) varieties, namely, Monthong and Chanee, were analyzed chemically to determine their total phenolic content (TPC), antioxidant, and anti-inflammatory capacities. Chanee pulp (CPu) contained a higher TPC (5285.37 ± 517.65 mg GAE/g) than Monthong pulp (MPu), Monthong peel (MP), Monthong seed (MS), Chanee peel (CP) and Chanee seed (CS) (p = 0.0027, 0.0042, 0.0229, 0.0069 and 0.36), respectively. The antioxidant activity of each durian extract was determined against ABTS, nitric oxide, superoxide, hydroxyl, and metal ions. The results indicated that the pulp, inner peel and seed of these durian varieties had antioxidant capacities. Murine Raw 264.7 macrophages were used to determine the cytotoxicity of the flour extracts. The extract of CS flour had the lowest cytotoxicity followed by MP, CPu, CP, MPu and MS (p = 0.5926, 0.44, 0.3191, 0.1471 and 0.0014), respectively. The anti-inflammatory activity was tested by anti-nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated cells by co-treating the Raw 264.7 cells with each durian flour extract and LPS. The extract of MP flour had the lowest IC50 against NO production, indicating the highest anti-NO production activity followed by CS, CPu, MPu, CP and MS (p = 0.7473, 0.0104, < 0.0001, 0.0002 and < 0.0001, respectively). The information obtained in this study is useful for researchers to explore more durian varieties in Southeast Asia to find bioactive compounds that might be novel nutraceuticals for antioxidant, anti-inflammation and therapeutic functional food

Positron Emission Tomography Radiopharmaceuticals in Differentiated Thyroid Cancer

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current hybrid scanner performing single photon emission tomography/computed tomography (SPECT/CT). Positron emission tomography/computed tomography (PET/CT) provides superior visualization and quantification of functions at the molecular level; thus, lesion assessment can be improved compared to that of SPECT/CT. Various types of cancer, including radioiodine-refractory DTC, can be detected by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most well-known and widely used PET radiopharmaceutical. Several other PET radiopharmaceuticals have been developed, although some are limited in availability despite their potential clinical utilizations. This article aims to summarize PET radiopharmaceuticals in DTC, focusing on molecular pathways and applications

Effect of Aqueous n-Butanol Treatments on Shelf-Life Extension of Longkong Fruit during Ambient Storage

The pericarp of the Longkong fruit rapidly browns during ambient storage, typically reducing its shelf life to between 3 and 7 days. Recently, n-butanol has demonstrated a promising effect in preventing this deterioration, extending the shelf life of tropical fruits to more than a week. The present study exploited this opportunity to examine the exogenous application of aqueous n-butanol at various concentrations (0.2–0.6%) in controlling pericarp browning and suppressing different oxidoreductase enzymes in the pericarp under prolonged ambient storage conditions (8 days). Every two days, the fruit pericarps were tested for color (lightness (L*), redness (a*), and yellowness (b*)), browning index (BI), membrane permeability loss (MPL), malondialdehyde (MDA) content, total phenolic content (TPC), and reactive oxygen species (ROS). Enzymes including phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), phospholipase D (PLD), lipoxygenase (LOX), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also analyzed. All sample test results showed that increased storage significantly impacted color characteristics (decreased L*, b* and increased a*, and BI). MPL, MDA, and ROS also continuously increased. Furthermore, the browning-related enzymes (PAL and PPO), membrane-degrading enzymes (PLD and LOX), and antioxidant enzymes (SOD, CAT, and GPX) continuously increased in all pericarp samples throughout the storage. Among the samples, pericarp color, BI, MPL, MDA, PAL, PPO, PLD, and LOX were significantly high in the control samples, consequently adversely affecting the quality and shelf life of Longkong. On the other hand, the n-butanol-treated samples significantly controlled the loss and all problematic enzymes while improving the activities of SOD, CAT, and GPX in the pericarp. Furthermore, the positive effect of n-butanol application was dose-dependent; higher concentrations (0.4–0.6%) performed well in protecting the fruit from deterioration