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Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles
摘要： Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. UCNP applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb,Er,Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin9-29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, non-cytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.
关键词： nanotoxicology,pharmacodynamics,pharmacokinetics,animal imaging,upconversion nanoparticles,photoluminescent nanomaterials
更新于2025-11-21 11:08:12
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Preserving preclinical PET quality during intratherapeutic imaging in radionuclide therapy with Rose metal shielding reducing photon flux
摘要： Performing Positron Emission Tomography (PET) imaging intratherapeutically during ongoing radionuclide therapy, can be a promising method to follow tumor response in vivo. However, the high therapeutic activity can interfere with the PET camera performance and degrade both image quality and quantitative capabilities. As a solution, low energy photon emissions from the therapeutic radionuclide can be highly attenuated, still allowing sufficient detection of annihilation photons in coincidence. Method: Hollow Rose metal cylinders with 2‐4 mm walls were used to shield a 22Na point source and a uniform phantom filled with 18F as they were imaged on a pre‐clinical PET camera with increasing activities of 177Lu. A mouse with a subcutaneous tumor was injected with 18F‐FDG and imaged with an additional 120 MBq of 177Lu and repeated with shields surrounding the animal. Results: The addition of 177Lu to the volume imaged continuously degraded the image quality with increasing activity. The image quality was improved when shielding was introduced. The shields showed a high ability to produce stable and reproducible results of both spatial resolution and activity quantification up to 120 MBq of 177Lu activity (maximum activity tested). Conclusion: Without shielding, the activity quantification will be inaccurate at time points where therapeutic activities are high. The suggested method shows that the shields reduce the noise induced by the 177Lu and therefore enables longitudinal quantitative intratherapeutic imaging studies.
关键词： small animal imaging,shielding,count losses,radionuclide therapy,PET
更新于2025-09-10 09:29:36
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A new High-Resolution Imaging System (HiRIS2) detector for preclinical SPECT imaging
摘要： The aim of the work is to describe a new high-performance scintigraphic detector, derived from our previous work based on a Position Sensitive Photomultiplier Tube (PSPMT) with 256 output anodes. This detector is suitable for direct integration into multi-modality imaging systems. Indeed, the detector has been developed in order to be integrated into a pre-clinical system. The detector is based on an H9500 Hamamatsu PSPMT coupled to an LYSO pixelated scintillator and a low-energy tungsten collimator with parallel square holes. In order to limit the overall size of the device, a dedicated compact electronics has been developed. The device design was performed using Monte Carlo transport calculations to aid the development. Our results show a detector performance suitable for application on small animals. The intrinsic spatial resolution was experimentally determined to be about 1.6 mm. The measured energy resolution was ～16% at 140 keV and the maximum recorded sensitivity was ～76 cps/MBq. In addition, the results agree quite well with those of Monte Carlo simulations. We have successfully improved the performance of our previous detector design in order to integrate the new device into a complex system focused on pre-clinical imaging.
关键词： Position sensitive photomultiplier tube,GATE,Scintigraphic small animal imaging,Single photon emission,SPECT
更新于2025-09-04 15:30:14