Fate of perfluorochemicals in animals after intravenous injection or hemodilution with their emulsions.

Yokoyama, Kazumasa; Yamanouchi, Kouichi; Ohyanagi, Harumasa; Mitsuno, Takao

doi:10.1248/cpb.26.956

Cited by 31 publications

(5 citation statements)

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“…Despite the high PFC doses used, we determined PFD halflives comparable with those reported in the literature (18,40,41). Surprisingly, signal intensities for PFD in the liver and spleen were found to be three orders of magnitude lower when compared with the other PFCs, which cannot be solely explained by methodological factors.…”

Section: Discussionsupporting

confidence: 74%

Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity

et al. 2013

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Inflammatory processes can reliably be assessed by (19)F MRI using perfluorocarbons (PFCs), which is primarily based on the efficient uptake of emulsified PFCs by circulating cells of the monocyte-macrophage system and subsequent infiltration of the (19)F-labeled cells into affected tissue. An ideal candidate for the sensitive detection of fluorine-loaded cells is the biochemically inert perfluoro-15-crown-5 ether (PFCE), as it contains 20 magnetically equivalent (19)F atoms. However, the biological half-life of PFCE in the liver and spleen is extremely long, and so this substance is not suitable for future clinical applications. In the present study, we investigated alternative, nontoxic PFCs with predicted short biological half-lives and high fluorine content: perfluorooctyl bromide (PFOB), perfluorodecalin (PFD) and trans-bis-perfluorobutyl ethylene (F-44E). Despite the complex spectra of these compounds, we obtained artifact-free images using sine-squared acquisition-weighted three-dimensional chemical shift imaging and dedicated reconstruction accomplished with in-house-developed software. The signal-to-noise ratio of the images was maximized using a Nutall window with only moderate localization error. Using this approach, the retention times of the different PFCs in murine liver and spleen were determined at 9.4 T. The biological half-lives were estimated to be 9 days (PFD), 12 days (PFOB) and 28 days (F-44E), compared with more than 250 days for PFCE. In vivo sensitivity for inflammation imaging was assessed using an ear clip injury model. The alternative PFCs PFOB and F-44E provided 37% and 43%, respectively, of the PFCE intensities, whereas PFD did not show any signal in the ear model. Thus, for in vivo monitoring of inflammatory processes, PFOB emerges as the most promising candidate for possible future translation of (19)F MR inflammation imaging to human applications.

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Section: Discussionsupporting

confidence: 74%

Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity

et al. 2013

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“…With a target hematocrit of 5% we have purposely gone below this critical hematocrit to make the effects of a deficient oxygen supply obviously visible in the control animals. Similar approaches were performed in other studies evaluating novel AOCs 21 – 23 .…”

Section: Discussionmentioning

confidence: 83%

Albumin-derived perfluorocarbon-based artificial oxygen carriers can avoid hypoxic tissue damage in massive hemodilution

Wrobeln

Jägers

Quinting

et al. 2020

Sci Rep

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Artificial blood for clinical use is not yet available therefore, we previously developed artificial oxygen carriers (capsules) and showed their functionality in vitro and biocompatibility in vivo. Herein, we assessed the functionality of the capsules in vivo in a normovolemic hemodilution rat-model. We stepwise exchanged the blood of male Wistar-rats with medium either in the presence of capsules (treatment) or in their absence (control). We investigated tissue hypoxia thoroughly through online biomonitoring, determination of enzyme activity and pancreatic hormones in plasma, histochemical and immunohistochemical staining of small intestine, heart, liver and spleen as well as in situ hybridization of kidneys. After hemodilution, treated animals show higher arterial blood pressure and have a stable body temperature. Additionally, they show a more stable pH, a higher oxygen partial pressure (pO 2), and a lower carbon dioxide partial pressure (pCO 2). Interestingly, blood-glucose-levels drop severely in treated animals, presumably due to glucose consumption. Creatine kinase values in these animals are increased and isoenzyme analysis indicates the spleen as origin. Moreover, the small intestine of treated animals show reduced hypoxic injury compared to controls and the kidneys have reduced expression of the hypoxia-inducible erythropoietin mRNA. In conclusion, our capsules can prevent hypoxic tissue damage. The results provide a proof of concept for capsules as adequate erythrocyte substitute. The need to develop synthetic products for blood replacement has become more and more important during the last decades. On the one hand, the demographic change leads to increasing requirements for blood, and on the other hand, simultaneously the willingness for blood donation declines 1. Blood with its various characteristics fulfils many functions, recent developments of synthetic blood substitutes focus on its most important function: the transport of physiological gases, in particular of oxygen. Additional key requirements for artificial blood substitutes are optimal size, sterility, biocompatibility, and the ability to be stored without loss of functionality. Moreover, artificial oxygen carriers (AOCs) should have a long intravascular circulation time and universal usage independent of the blood group characteristics 2,3. There are two main approaches to realize the transport of essential gases. The first is the use of the physiological oxygen carrier hemoglobin (hemoglobin-based artificial oxygen carriers, HBOCs); a concept realized e.g. in the prominent product hemopure, that gained pharmaceutical approval in South Africa and Mexico. Further HBOCs (e.g. sanguinate) are currently tested in clinical trials 4. So far, most of the products showed severe side effects so that the manufacturing had to be stopped 5. The second is the work with synthetic materials like perfluorocarbons [perfluorocarbon-based artificial oxygen carriers (PFOCs)]. Depending on the actual partial pressure, PFOCs are able to solve gases physically 6...

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“…Numerous studies have focused on the intravascular persistence, in vivo distribution, and excretion of PFCs. ,,,,,,,− In short, the PFC droplets infused in the vasculature are opsonized (i.e., made recognizable by the binding of specific plasma proteins, the opsonins), progressively phagocytized by circulating monocytes and fixed macrophages of the RES, the larger droplets being removed first. This mechanism is largely responsible for the limited intravascular half-life of the emulsions.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

2001

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Pharmaceutical Corporation in San Diego; however, the opinion expressed here are solely his and not necessarily those of the Corporation. Jean G. Riess received his chemical engineer and doctorat-e `s-sciences degrees (the latter with Professor Guy Ourisson in 1963) from the University of Strasbourg. He then spent two years with John Van Wazer at Monsanto in Saint-Louis, MO, learning some phosphorus and transitionmetal chemistry. In 1968 he became Professor at the University of Nice, France, where he founded, directed, and eventually became honorary director of the Unite ´de Chimie Mole ´culaire (associated with the Centre National de la Recherche Scientifique). His research successively involved phosphorus chemistry, transition-metal chemistry, organometallics, and eventually perfluorochemicals. His present interests are in fluorocarbons, fluorinated amphiphiles, and their colloid chemistry, including fluorocarbon emulsions for in vivo O 2 delivery, fluorinated self-assemblies, and drug delivery systems. Professor Riess has published about 360 papers and holds ca. 25 patents. He has served on numerous councils and committees and has chaired or co-chaired international conferences on phosphorus chemistry and blood substitutes. He has won awards from the French Academy of Sciences, French Chemical Society, Alexander von Humboldt Stifftung, City of Nice and Controlled Release Society, as well as Alliance's first Distinguished Contribution Award. He holds an honorary Research Associate position at the University of California at San Diego and sits on the Board of Directors of Alliance Pharmaceutical Corp.

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Fate of perfluorochemicals in animals after intravenous injection or hemodilution with their emulsions.

Cited by 31 publications

References 0 publications

Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity

Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity

Albumin-derived perfluorocarbon-based artificial oxygen carriers can avoid hypoxic tissue damage in massive hemodilution

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

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Fate of perfluorochemicals in animals after intravenous injection or hemodilution with their emulsions.

Cited by 31 publications

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Probing different perfluorocarbons forin vivoinflammation imaging by19F MRI: image reconstruction, biological half-lives and sensitivity

Probing different perfluorocarbons forin vivoinflammation imaging by19F MRI: image reconstruction, biological half-lives and sensitivity

Albumin-derived perfluorocarbon-based artificial oxygen carriers can avoid hypoxic tissue damage in massive hemodilution

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

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Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity

Probing different perfluorocarbons forin vivoinflammation imaging by¹⁹F MRI: image reconstruction, biological half-lives and sensitivity