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

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.

scholarly journals Automated quantification of baseline imaging PET metrics on FDG PET/CT images of pediatric Hodgkin lymphoma patients

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Amy J. Weisman ◽  
Jihyun Kim ◽  
Inki Lee ◽  
Kathleen M. McCarten ◽  
Sandy Kessel ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Correlation Coefficient ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Relative Difference ◽  
Ct Images ◽  
Imaging Features ◽  
Pediatric Hodgkin Lymphoma ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Purpose For pediatric lymphoma, quantitative FDG PET/CT imaging features such as metabolic tumor volume (MTV) are important for prognosis and risk stratification strategies. However, feature extraction is difficult and time-consuming in cases of high disease burden. The purpose of this study was to fully automate the measurement of PET imaging features in PET/CT images of pediatric lymphoma. Methods 18F-FDG PET/CT baseline images of 100 pediatric Hodgkin lymphoma patients were retrospectively analyzed. Two nuclear medicine physicians identified and segmented FDG avid disease using PET thresholding methods. Both PET and CT images were used as inputs to a three-dimensional patch-based, multi-resolution pathway convolutional neural network architecture, DeepMedic. The model was trained to replicate physician segmentations using an ensemble of three networks trained with 5-fold cross-validation. The maximum SUV (SUVmax), MTV, total lesion glycolysis (TLG), surface-area-to-volume ratio (SA/MTV), and a measure of disease spread (Dmaxpatient) were extracted from the model output. Pearson’s correlation coefficient and relative percent differences were calculated between automated and physician-extracted features. Results Median Dice similarity coefficient of patient contours between automated and physician contours was 0.86 (IQR 0.78–0.91). Automated SUVmax values matched exactly the physician determined values in 81/100 cases, with Pearson’s correlation coefficient (R) of 0.95. Automated MTV was strongly correlated with physician MTV (R = 0.88), though it was slightly underestimated with a median (IQR) relative difference of − 4.3% (− 10.0–5.7%). Agreement of TLG was excellent (R = 0.94), with median (IQR) relative difference of − 0.4% (− 5.2–7.0%). Median relative percent differences were 6.8% (R = 0.91; IQR 1.6–4.3%) for SA/MTV, and 4.5% (R = 0.51; IQR − 7.5–40.9%) for Dmaxpatient, which was the most difficult feature to quantify automatically. Conclusions An automated method using an ensemble of multi-resolution pathway 3D CNNs was able to quantify PET imaging features of lymphoma on baseline FDG PET/CT images with excellent agreement to reference physician PET segmentation. Automated methods with faster throughput for PET quantitation, such as MTV and TLG, show promise in more accessible clinical and research applications.

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

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.

scholarly journals PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2289
Author(s):  
Naresh Damuka ◽  
Paul Czoty ◽  
Ashley Davis ◽  
Michael Nader ◽  
Susan Nader ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neurological Disorders ◽  
Healthy Male ◽  
Time Activity ◽  
Positron Emission ◽  
Pet Ct ◽  
Scan Data ◽  
The Brain ◽  
Human Primate

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

scholarly journals Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Radiochemical Yield ◽  
Control Group ◽  
Complexing Agent ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Pet Ct

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

In Vivo Verification of Dose Delivery to Prostate Cancer by Utilizing PET/CT Images Taken after Proton Therapy

2008 ◽  
Vol 72 (1) ◽  
pp. S144 ◽  
Author(s):  
L. Lin ◽  
W. Hsi ◽  
D. Indelicato ◽  
C. Vargas ◽  
S. Flampouri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proton Therapy ◽  
Ct Images ◽  
Dose Delivery ◽  
Pet Ct

scholarly journals Lo studio PET/TC delle placche ?-amiloidi con 18F – FlorBetapir, 18F – FlorBetaben e 18F – Flutemetamol

2019 ◽  
Author(s):  
Giovanni Trondoli ◽  
Dario Saffioti
Keyword(s):  
Cerebral Cortex ◽  
Basal Ganglia ◽  
Home Care ◽  
Pet Imaging ◽  
Cortical Neurons ◽  
Parietal Lobes ◽  
Pet Ct ◽  
Ct Analysis ◽  
Nello Studio

La malattia di Alzheimer uccide circa 53.000 persone all’anno e circa 230.000 soggetti affetti dalla patologia richiedono cure domiciliari. Questa patologia è caratterizzata microscopicamente dalla comparsa di sostanza amiloide a livello della corteccia cerebrale con diminuzione del numero di neuroni corticali, in particolare nei lobi frontali e temporo-parietali. Più nello specifico, colpisce alcune regioni encefaliche quali i nuclei della base, l’ippocampo e il giro dell’ippocampo, aree direttamente coinvolte nell’elaborazione dei ricordi. Negli ultimi anni, lo sviluppo dell’imaging PET ha reso possibile l’utilizzo di traccianti fluorati per lo studio della sostanza amiloide e la sua visualizzazione in vivo. I radiotraccianti più importanti nell’analisi PET/TC sono: l’Amyvid (18F - FlorBetapir), il Neuraceq (18F - FlorBetaben) e il Vizamyl (18F- Flutemetamol) che hanno evidenziato l’efficacia nello studio della sostanza amiloide. Alzheimer’s disease (AD) kills about 53.000 people every year and about 230.000 subjects affected by AD need home care. This disease is microscopically characterized 3 amyloid substance on cerebral cortex with a reduction of cortical neurons, in particular in frontal and temporo-parietal lobes; it damages particularly some encephalic regions such as basal ganglia, hippocampus and hippocampus gyrus, areas directly related to elaboration of memories. In the last years, the development of PET imaging has made possible the use of fluorinated tracers to study amyloid substance and its visualization in vivo. Amyvid (18F - FlorBetapir), Neuraceq (18F - FlorBetaben) and Vizamyl (18F - Flutemetamol) are the most important radiotracers for PET/CT analysis which have been underlined the efficacy in the study of amyloid substance.

scholarly journals Preclinical Evaluation of the Copper-64 Labeled GRPR-Antagonist RM26 in Comparison with the Cobalt-55 Labeled Counterpart for PET-Imaging of Prostate Cancer

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5993
Author(s):  
Christina Baun ◽  
Bogdan Mitran ◽  
Sara S. Rinne ◽  
Johan H. Dam ◽  
Birgitte B. Olsen ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Time ◽  
Vitro Binding ◽  
Pet Ct ◽  
Liver And Pancreas ◽  
Prostate Cancers ◽  
Grpr Antagonist ◽  
Late Time Point

Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of 64Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG2-RM26 and NODAGA-PEG2-RM26. Methods: NOTA/NODAGA-PEG2-RM26 were labeled with 64Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [57Co]Co-NOTA/NODAGA-PEG2-RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG2-RM26 were stably labeled with 64Cu with quantitative yields. In vitro, binding of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was rapid and GRPR-specific with slow internalization. In vivo, [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [57Co]Co-NOTA/NODAGA-PEG2-RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [64Cu]Cu-NOTA-PEG2-RM26 had a significantly higher liver and pancreas uptake compared to other agents. 57Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the 64Cu-labeled counterparts. [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [55/57Co]Co-NOTA/NODAGA-PEG2-RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the 64Cu-labeled conjugates.

[89Zr]Zr(oxinate)4 Allows Direct Radiolabelling and PET Imaging of Small Extracellular Vesicles

2021 ◽  
Author(s):  
Azalea Khan ◽  
Francis Man ◽  
Farid Faruqu ◽  
Jana Kim ◽  
Fahad Al-Salemee ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Pet Imaging ◽  
Ct Imaging ◽  
Pet Ct

89Zr]Zr(oxinate)4 allows direct radiolabelling of exosomes/small extracellular vesicles (sEVs) and in vivo PET-CT imaging

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