A mini-panel PET scanner-based microfluidic radiobioassay system allowing high-throughput imaging of real-time cellular pharmacokinetics

Liu, Zhen; Zhang, Pengfei; Ji, Hao; Liu, Yu; Jing, Boping; Xi, Daoming; An, Rui; Lan, Xiaoli

doi:10.1039/c9lc01066a

Cited by 11 publications

(10 citation statements)

References 55 publications

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“…Besides other NETs, also pancreatic NET can be diagnosed with [ 68 Ga]Ga-DOTATATE [ 185 ]. For radiopharmacists, the mini-panel PET scanner-based microfluidic radiobioassay system developed by Liu et al [ 186 ] is of interest. Microfluidic radiobioassays are assays using radiotracers to detect samples on chips.…”

Section: 3d Models As Radiopharmacists’ Tool For Development Of Ramentioning

confidence: 99%

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Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research

Doctor

Seifert

Ullrich

et al. 2020

Cancers

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In preclinical cancer research, three-dimensional (3D) cell culture systems such as multicellular spheroids and organoids are becoming increasingly important. They provide valuable information before studies on animal models begin and, in some cases, are even suitable for reducing or replacing animal experiments. Furthermore, they recapitulate microtumors, metastases, and the tumor microenvironment much better than monolayer culture systems could. Three-dimensional models show higher structural complexity and diverse cell interactions while reflecting (patho)physiological phenomena such as oxygen and nutrient gradients in the course of their growth or development. These interactions and properties are of great importance for understanding the pathophysiological importance of stromal cells and the extracellular matrix for tumor progression, treatment response, or resistance mechanisms of solid tumors. Special emphasis is placed on co-cultivation with tumor-associated cells, which further increases the predictive value of 3D models, e.g., for drug development. The aim of this overview is to shed light on selected 3D models and their advantages and disadvantages, especially from the radiopharmacist’s point of view with focus on the suitability of 3D models for the radiopharmacological characterization of novel radiotracers and radiotherapeutics. Special attention is paid to pancreatic ductal adenocarcinoma (PDAC) as a predestined target for the development of new radionuclide-based theranostics.

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Section: 3d Models As Radiopharmacists’ Tool For Development Of Ramentioning

confidence: 99%

“…Microfluidic radiobioassays are assays using radiotracers to detect samples on chips. Liu et al [ 186 ] extended this approach with the use of PET to detect the radiopharmacokinetics in 3D models.…”

Section: 3d Models As Radiopharmacists’ Tool For Development Of Ramentioning

confidence: 99%

Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research

Doctor

Seifert

Ullrich

et al. 2020

Cancers

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“…For the imaging of PET tracers, conventional 3D preclinical scanners are not optimal for imaging of thin tissue within the observation window due to low intrinsic resolution and partial volume effects (PVE) [32]. The positron camera has an intrinsically higher resolution of 230 μm for 2D imaging [22,23], which is better than the intrinsic resolution of typical 3D preclinical PET scanners [33,34,35]. In practice, positron imaging is not perfect 2D imaging either and measures the superposed signals from tissues close to the contacting surface.…”

Section: Multimodal Molecular Imagingmentioning

confidence: 99%

Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

Liu

Cheng

Düwel

et al. 2021

Eur J Nucl Med Mol Imaging

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Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

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“…5). A recent example is a continuously infused microfluidic radioassay with a miniaturized PET scanner for microfluidics-based radiobioassays with a wide range of applications such as evaluations of organoids, clinical samples, and lab-on-a-chip studies (40).…”

Section: New Indications For MImentioning

confidence: 99%