O. Ivashchenko
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6 records found
1
Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and circulation time of nanocarriers using polystyrene-b-poly(ethylene oxide) micelles of spherical or elongated morphology. The glassy nature of polystyrene guarantees the morphological stability of the carriers in vivo and by encapsulating Indium-111 in their core, an assessment of the longitudinal in vivo biodistribution of the particles in healthy mice is performed with single photon emission computed tomography imaging. Our results show prolonged blood circulation, longer than 24 hours, for all micelle morphologies studied. Dynamics of micelle accumulation in the liver and other organs of the reticuloendothelial system show a size-dependent nature and late stage liver clearance is observed for the elongated morphology. Apparent contradictions between recent similar studies can be resolved by considering the effects of flexibility and degradation of the elongated micelles on their circulation time and biodistribution.
Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of 111In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.
High-resolution pre-clinical 131I SPECT can facilitate development of new radioiodine therapies for cancer. To this end, it is important to limit resolution-degrading effects of pinhole edge penetration by the high-energy γ-photons of iodine. Here we introduce, optimize and validate 131I SPECT performed with a dedicated high-energy clustered multi-pinhole collimator.
Methods
A SPECT–CT system (VECTor/CT) with stationary gamma-detectors was equipped with a tungsten collimator with clustered pinholes. Images were reconstructed with pixel-based OSEM, using a dedicated 131I system matrix that models the distance- and energy-dependent resolution and sensitivity of each pinhole, as well as the intrinsic detector blurring and variable depth of interaction in the detector. The system performance was characterized with phantoms and in vivo static and dynamic 131I-NaI scans of mice.
Results
Reconstructed image resolution reached 0.6 mm, while quantitative accuracy measured with a 131I filled syringe reaches an accuracy of + 3.6 ± 3.5% of the gold standard value. In vivo mice scans illustrated a clear shape of the thyroid and biodistribution of 131I within the animal. Pharmacokinetics of 131I was assessed with 15-s time frames from the sequence of dynamic images and time–activity curves of 131I-NaI.
Conclusions
High-resolution quantitative and fast dynamic 131I SPECT in mice is possible by means of a high-energy collimator and optimized system modeling. This enables analysis of 131I uptake even within small organs in mice, which can be highly valuable for development and optimization of targeted cancer therapies. ...
High-resolution pre-clinical 131I SPECT can facilitate development of new radioiodine therapies for cancer. To this end, it is important to limit resolution-degrading effects of pinhole edge penetration by the high-energy γ-photons of iodine. Here we introduce, optimize and validate 131I SPECT performed with a dedicated high-energy clustered multi-pinhole collimator.
Methods
A SPECT–CT system (VECTor/CT) with stationary gamma-detectors was equipped with a tungsten collimator with clustered pinholes. Images were reconstructed with pixel-based OSEM, using a dedicated 131I system matrix that models the distance- and energy-dependent resolution and sensitivity of each pinhole, as well as the intrinsic detector blurring and variable depth of interaction in the detector. The system performance was characterized with phantoms and in vivo static and dynamic 131I-NaI scans of mice.
Results
Reconstructed image resolution reached 0.6 mm, while quantitative accuracy measured with a 131I filled syringe reaches an accuracy of + 3.6 ± 3.5% of the gold standard value. In vivo mice scans illustrated a clear shape of the thyroid and biodistribution of 131I within the animal. Pharmacokinetics of 131I was assessed with 15-s time frames from the sequence of dynamic images and time–activity curves of 131I-NaI.
Conclusions
High-resolution quantitative and fast dynamic 131I SPECT in mice is possible by means of a high-energy collimator and optimized system modeling. This enables analysis of 131I uptake even within small organs in mice, which can be highly valuable for development and optimization of targeted cancer therapies.
METHODS:
A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans.
RESULTS:
The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter megabecquerel of activity, 30-min bone SPECT scans provided surprisingly high levels of detail. Dynamic dual-isotope kidney and (99m)Tc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s.
CONCLUSION:
The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics. ...
METHODS:
A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans.
RESULTS:
The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter megabecquerel of activity, 30-min bone SPECT scans provided surprisingly high levels of detail. Dynamic dual-isotope kidney and (99m)Tc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s.
CONCLUSION:
The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics.