Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo Cell Trafficking by PET/CT

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

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Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors

EJNMMI Research ◽

10.1186/s13550-021-00752-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoichi Shimizu ◽

Yukihiro Nakai ◽

Hiroyuki Watanabe ◽

Shimpei Iikuni ◽

Masahiro Ono ◽

...

Keyword(s):

Cyclosporine A ◽

Pet Imaging ◽

Multidrug Resistant ◽

Ct Images ◽

Pet Scan ◽

Reduced Form ◽

Pet Ct ◽

Fadu Cells ◽

Hypoxic State

Abstract Background [18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [18F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [18F]FMISO PET imaging. Methods FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [18F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [18F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). Results FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05). Conclusion In this study, we revealed that MRP1 inhibitors increase [18F]FMISO accumulation in hypoxic cells. This suggests that [18F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.

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Vitamin D3-mediated alterations to myeloid dendritic cell trafficking in vivo expand the scope of their antigen presenting properties

Vaccine ◽

10.1016/j.vaccine.2006.10.008 ◽

2007 ◽

Vol 25 (7) ◽

pp. 1236-1249 ◽

Cited By ~ 17

Author(s):

Elena Y. Enioutina ◽

Diana Bareyan ◽

Raymond A. Daynes

Keyword(s):

Dendritic Cell ◽

Vitamin D3 ◽

Cell Trafficking ◽

Myeloid Dendritic Cell ◽

Antigen Presenting ◽

Dendritic Cell Trafficking

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The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration

Blood ◽

10.1182/blood-2008-07-167668 ◽

2009 ◽

Vol 113 (24) ◽

pp. 6138-6147 ◽

Cited By ~ 66

Author(s):

Audrey Gérard ◽

Rob A. van der Kammen ◽

Hans Janssen ◽

Saskia I. Ellenbroek ◽

John G. Collard

Keyword(s):

T Cells ◽

Endothelial Cells ◽

T Cell ◽

Transendothelial Migration ◽

Contact Hypersensitivity ◽

Cell Trafficking ◽

T Cell Trafficking ◽

Cell Arrest

Abstract Migration toward chemoattractants is a hallmark of T-cell trafficking and is essential to produce an efficient immune response. Here, we have analyzed the function of the Rac activator Tiam1 in the control of T-cell trafficking and transendothelial migration. We found that Tiam1 is required for chemokine- and S1P-induced Rac activation and subsequent cell migration. As a result, Tiam1-deficient T cells show reduced chemotaxis in vitro, and impaired homing, egress, and contact hypersensitivity in vivo. Analysis of the T-cell transendothelial migration cascade revealed that PKCζ/Tiam1/Rac signaling is dispensable for T-cell arrest but is essential for the stabilization of polarization and efficient crawling of T cells on endothelial cells. T cells that lack Tiam1 predominantly transmigrate through individual endothelial cells (transcellular migration) rather than at endothelial junctions (paracellular migration), suggesting that T cells are able to change their route of transendothelial migration according to their polarization status and crawling capacity.

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Ultrasound-based sensors for respiratory motion assessment in multimodality PET imaging

Physics in Medicine and Biology ◽

10.1088/1361-6560/ac4213 ◽

2021 ◽

Author(s):

Bruno Madore ◽

Gabriela Belsley ◽

Cheng-Chieh Cheng ◽

Frank Preiswerk ◽

Marie Foley Kijewski ◽

...

Keyword(s):

Pet Imaging ◽

Respiratory Gating ◽

Sensitive Information ◽

Internal Organs ◽

Respiration Monitoring ◽

Breathing Motion ◽

Pet Ct ◽

Motion Phantom ◽

Motion Assessment

Abstract Breathing motion can displace internal organs by up to several cm; as such, it is a primary factor limiting image quality in medical imaging. Motion can also complicate matters when trying to fuse images from different modalities, acquired at different locations and/or on different days. Currently available devices for monitoring breathing motion often do so indirectly, by detecting changes in the outline of the torso rather than the internal motion itself, and these devices are often fixed to floors, ceilings or walls, and thus cannot accompany patients from one location to another. We have developed small ultrasound-based sensors, referred to as ‘organ configuration motion’ (OCM) sensors, that attach to the skin and provide rich motion-sensitive information. In the present work we tested the ability of OCM sensors to enable respiratory gating during in vivo PET imaging. A motion phantom involving an FDG solution was assembled, and two cancer patients scheduled for a clinical PET/CT exam were recruited for this study. OCM signals were used to help reconstruct phantom and in vivo data into time series of motion-resolved images. As expected, the motion-resolved images captured the underlying motion. In Patient #1, a single large lesion proved to be mostly stationary through the breathing cycle. However, in Patient #2, several small lesions were mobile during breathing, and our proposed new approach captured their breathing-related displacements. In summary, a relatively inexpensive hardware solution was developed here for respiration monitoring. Because the proposed sensors attach to the skin, as opposed to walls or ceilings, they can accompany patients from one procedure to the next, potentially allowing data gathered in different places and at different times to be combined and compared in ways that account for breathing motion.

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Discordance between Histopathological grading and Dual Tracer PET-CT findings (68Ga-DOTATATE and FDG) in metastatic Neuroendocrine Neoplasms and outcome of 177Lu-DOTATATE PRRT: does in-vivo molecular PET imaging perform better from ‘prediction of tumour biology’ viewpoint?

Journal of Nuclear Medicine Technology ◽

10.2967/jnmt.121.261998 ◽

2021 ◽

pp. jnmt.121.261998

Author(s):

Aadil Adnan ◽

Sandip Basu

Keyword(s):

Pet Imaging ◽

Neuroendocrine Neoplasms ◽

Ct Findings ◽

Tumour Biology ◽

Pet Ct ◽

Histopathological Grading ◽

Dual Tracer

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Erratum to: Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F–DOPA

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-017-3807-0 ◽

2017 ◽

Vol 44 (12) ◽

pp. 2150-2151 ◽

Cited By ~ 1

Author(s):

Murat Fani Bozkurt ◽

Irene Virgolini ◽

Sona Balogova ◽

Mohsen Beheshti ◽

Domenico Rubello ◽

...

Keyword(s):

Somatostatin Receptor ◽

Ct Imaging ◽

Neuroendocrine Neoplasms ◽

Receptor Targeting ◽

Pet Ct

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Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases

Frontiers in Oncology ◽

10.3389/fonc.2021.795712 ◽

2022 ◽

Vol 11 ◽

Author(s):

Chuan-Yu Sun ◽

Yuan-Yuan Mi ◽

Sheng-Yang Ge ◽

Qing-Feng Hu ◽

Ke Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Integrin Αvβ3 ◽

Integrin Receptors ◽

Secreted Expression ◽

Metastatic Lesions ◽

Promising Therapeutic Target ◽

Pet Ct

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvβ3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

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