Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics

Nanocarriers encapsulating nucleic acids or protein therapeutics are important tools for modulating biodistribution and enhancing intracellular delivery of biologics. We have recently developed inverse Flash NanoPrecipitation (iFNP), demonstrating its effectiveness in encapsulating biologics at high loadings and encapsulation efficiency. Here, we present the biodistribution of two iFNP nanocarriers using 64Cu positron emission tomography imaging in a murine adenocarcinoma xenograft model characterized by elevated macrophage content. Two nanocarriers with similar sizes and surfaces were prepared. iFNP produces core-shell-corona nanocarriers where the hydrophobic shell layer in one case was poly(lactic acid) (PLA), and the other nanocarrier shell was poly(styrene) (PS). While the expectation was that the biodistribution and clearance of both nanocarriers would be similar, it was found that the clearance of the PS nanocarrier oc-curred in less than 3 hours while the PLA nanocarrier exhibited sustained circulation times. The mechanism of nanocarrier instability for the PS shell nanocarrier manifests as the development of a negative surface charge due to the exposure of the anionic nanocarrier inner core. The stable PLA-based formulation exhibited circulation times greater than 24 hours and enhanced accumu-lation in the lymphatics and the tumor relative to the unstable formulation. The novel mecha-nism of encapsulation by iFNP motivates the fundamental studies on nanoparticle biodistribu-tion reported here

NEMA NU 4-2008 Comparison of preclinical PET imaging systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of smallanimal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: micro- PET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.This work was funded by the Natural Sciences and Engineering Research Council of Canada under Discovery Grant 341628-2007. No other potential conflict of interest relevant to this article was reported.En prens

Post Mortem Study on the Effects of Routine Handling and Manipulation of Laboratory Mice

Routine handling and manipulation of laboratory mice are integral components of most preclinical studies. Any type of handling and manipulation may cause stress and result in physical harm to mice, potentially leading to unintended consequences of experimental outcomes. Nevertheless, the pathological effects of these interventions are poorly documented and assumed to have a negligible effect on experimental variables. In that context, we provide a comprehensive post mortem overview of the main pathological changes associated with routine interventions (i.e., restraint, blood drawing, and intraperitoneal injections) of laboratory mice with an emphasis on presumed traumatic osteoarticular lesions. A total of 1000 mice from various studies were included, with 864 animals being heavily manipulated and 136 being handled for routine husbandry procedures only. The most common lesions observed were associated with blood collection or intraperitoneal injections, as well as a series of traumatic osteoarticular lesions likely resulting from restraint. Osteoarticular lesions were found in 62 animals (61 heavily manipulated; 1 unmanipulated) with rib fractures and avulsion of the dens of the axis being over-represented. Histopathology and micro-CT confirmed the traumatic nature of the rib fractures. While these lesions might be unavoidable if mice are manipulated according to the current standards, intentional training of research personnel on appropriate mouse handling and restraint techniques could help reduce their frequency and the impact on animal wellbeing as well as study reproducibility