Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd 3+ with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd 3+ MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications.
Conventional storage of platelet concentrates limits their shelf life to between 5 and 7 days due to the risk of bacterial proliferation and the development of the platelet storage lesion. Cold storage and cryopreservation of platelets may facilitate extension of the shelf life to weeks and years, and may also provide the benefit of being more haemostatically effective than conventionally stored platelets. Further, treatment of platelet concentrates with pathogen inactivation systems reduces bacterial contamination and provides a safeguard against the risk of emerging and re-emerging pathogens. While each of these alternative storage techniques is gaining traction individually, little work has been done to examine the effect of combining treatments in an effort to further improve product safety and minimize wastage. This review aims to discuss the benefits of alternative storage techniques and how they may be combined to alleviate the problems associated with conventional platelet storage.
Background and Objectives Refrigeration (cold‐storage) of pathogen inactivated (PI) platelet components may increase the shelf‐life and safety profile of platelet components, compared to conventional room‐temperature (RT) storage. Whilst there is substantial knowledge regarding the impact of these individual treatments on platelets, the combined effect has not been assessed. Materials and methods Using a pool‐and‐split study design, paired buffy‐coat derived platelets in 70% platelet additive solution (SSP+; MacoPharma) were left untreated or PI‐treated using the THERAFLEX UV‐Platelets System (UVC; MacoPharma). Units from each pair were split and stored at room temperature (20–24°C) or cold‐stored (2–6°C) to yield RT, cold, RT‐UVC and cold‐UVC study groups (n = 8 in each group). In vitro quality and function was tested over 9 days. Results Cold‐storage of UVC‐treated platelets reduced glycolytic metabolism (glucose consumption and lactate production) compared to RT‐UVC units. Cold‐UVC platelets demonstrated complete abrogation of HSR by day 5, increased externalisation of phosphatidylserine (annexin‐V binding) and activation of the GPIIb/IIIa receptor (PAC‐1 binding) above the levels observed with the individual treatments. Aggregation responses (ADP and collagen) were enhanced in the cold‐UVC platelets compared to both RT groups, but this was primarily mediated by cold‐storage. Haemostatic function, as measured using TEG, was similar between the groups. Conclusion Cold‐storage of UVC‐treated platelets reduced PI‐induced acceleration of glycolytic metabolism. However, combining cold‐storage and UVC‐treatment resulted in additional phenotypic changes compared to each treatment individually. Further work is required to understand the impact of these changes in clinical efficacy.
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