In vivo clearance of 19F MRI imaging nanocarriers is strongly influenced by nanoparticle ultrastructure

Staal, Alexander H.J.; Becker, K.; Tagit, Oya; Riessen, N. Koen van; Koshkina, Olga; Veltien, Andor; Bouvain, Pascal; Cortenbach, Kimberley R.G.; Scheenen, Tom W. J.; Flögel, Ulrich; Temme, Sebastian; Srinivas, Mangala

doi:10.1016/j.biomaterials.2020.120307

Cited by 38 publications

(62 citation statements)

References 62 publications

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“…The biodistribution of the [ 89 Zr]Zr-PLGA-NH 2 NPs was in line with our previous observations with [ 111 In]In-PLGA-NH 2 NPs [34]. The signal at the tail was probably due to partial s.c. injection of the NPs.…”

Section: Discussionsupporting

confidence: 90%

In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Krekorian

Cortenbach

Boswinkel

et al. 2021

Cancers

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The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. 111In-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([111In]In-PLGA-NH2 NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed 89Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH2 NPs with [89Zr]ZrCl4. In vitro, [89Zr]Zr-PLGA-NH2 NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 ± 10 kBq/106 cells). PET/MRI imaging could detect low numbers of [89Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [89Zr]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular Staphylococcus aureus infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [89Zr]Zr-PLGA-NH2 NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models.

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Section: Discussionsupporting

confidence: 90%

In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Krekorian

Cortenbach

Boswinkel

et al. 2021

Cancers

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“…However, also PFC transit to the gut has been observed, but this seems to be of minor relevance for humans and non-rodent species 49 . Importantly, there are recent reports about quickly clearing and more sustainable PFC formulations 50 , 51 , which will be helpful for bridging the gap between experimental animal studies and human applications. Nevertheless, doses and biological half-lives have to be specifically tailored for human use, but this is clearly beyond the scope of the present study and has to be adjusted in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Multi-targeted 1H/19F MRI unmasks specific danger patterns for emerging cardiovascular disorders

et al. 2021

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Prediction of the transition from stable to acute coronary syndromes driven by vascular inflammation, thrombosis with subsequent microembolization, and vessel occlusion leading to irreversible myocardial damage is still an unsolved problem. Here, we introduce a multi-targeted and multi-color nanotracer platform technology that simultaneously visualizes evolving danger patterns in the development of progressive coronary inflammation and atherothrombosis prior to spontaneous myocardial infarction in mice. Individual ligand-equipped perfluorocarbon nanoemulsions are used as targeting agents and are differentiated by their specific spectral signatures via implementation of multi chemical shift selective 19F MRI. Thereby, we are able to identify areas at high risk of and predictive for consecutive development of myocardial infarction, at a time when no conventional parameter indicates any imminent danger. The principle of this multi-targeted approach can easily be adapted to monitor also a variety of other disease entities and constitutes a technology with disease-predictive potential.

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“…Molecules with incorporated Fluorine-19 ( 19 F) receive much interest as Magnetic Resonance Imaging (MRI) contrast agents in heteronuclear or hot-spot imaging [1][2][3]. With 19 F MRI, background-free in vivo images can be acquired, which can be combined with conventional proton MRI for precise anatomical localization. Moreover, the 19 F signal is unambiguous; the signal measured is linear to the concentration of the imaging agent [4], and allows for quantification from the image data [5].…”

Section: Introductionmentioning

confidence: 99%

“…With 19 F MRI, background-free in vivo images can be acquired, which can be combined with conventional proton MRI for precise anatomical localization. Moreover, the 19 F signal is unambiguous; the signal measured is linear to the concentration of the imaging agent [4], and allows for quantification from the image data [5]. This differentiates heteronuclear contrast agents from conventional contrast agents, such as gadolinium chelates and super paramagnetic iron oxide particles, which create contrast by altering the existing signal [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…

Isoflurane (ISO) is the most commonly used preclinical inhalation anesthetic. This is a problem in 19 F MRI of fluorine contrast agents, as ISO signals cause artifacts that interfere with unambiguous image interpretation and quantification; the two most attractive properties of heteronuclear MRI. We aimed to avoid these artifacts using MRI strategies that can be applied by any pre-clinical researcher.

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19F MRI Imaging Strategies to Reduce Isoflurane Artifacts in In Vivo Images

et al. 2021

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Purpose Isoflurane (ISO) is the most commonly used preclinical inhalation anesthetic. This is a problem in 19F MRI of fluorine contrast agents, as ISO signals cause artifacts that interfere with unambiguous image interpretation and quantification; the two most attractive properties of heteronuclear MRI. We aimed to avoid these artifacts using MRI strategies that can be applied by any pre-clinical researcher. Procedures Three strategies to avoid ISO chemical shift displacement artifacts (CSDA) in 19F MRI are described and demonstrated with measurements of 19F-containing agents in phantoms and in vivo (n = 3 for all strategies). The success of these strategies is compared to a standard Rapid Acquisition with Relaxation Enhancement (RARE) sequence, with phantom and in vivo validation. ISO artifacts can successfully be avoided by (1) shifting them outside the region of interest using a narrow signal acquisition bandwidth, (2) suppression of ISO by planning a frequency-selective suppression pulse before signal acquisition or by (3) preventing ISO excitation with a 3D sequence with a narrow excitation bandwidth. Results All three strategies result in complete ISO signal avoidance (p < 0.0001 for all methods). Using a narrow acquisition bandwidth can result in loss of signal to noise ratio and distortion of the image, and a frequency-selective suppression pulse can be incomplete when B1-inhomogeneities are present. Preventing ISO excitation with a narrow excitation pulse in a 3D sequence yields the most robust results (relative SNR 151 ± 28% compared to 2D multislice methods, p = 0.006). Conclusion We optimized three easily implementable methods to avoid ISO signal artifacts and validated their performance in phantoms and in vivo. We make recommendation on the parameters that pre-clinical studies should report in their method section to make the used approach insightful.

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In vivo clearance of 19F MRI imaging nanocarriers is strongly influenced by nanoparticle ultrastructure

Cited by 38 publications

References 62 publications

In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Multi-targeted 1H/19F MRI unmasks specific danger patterns for emerging cardiovascular disorders

19F MRI Imaging Strategies to Reduce Isoflurane Artifacts in In Vivo Images

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