positron emission tomography imaging
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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon Klingler ◽  
Jason P. Holland

AbstractClinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.


PET Clinics ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. 31-39
Author(s):  
Cheryl Beegle ◽  
Navid Hasani ◽  
Roberto Maass-Moreno ◽  
Babak Saboury ◽  
Eliot Siegel

2021 ◽  
Author(s):  
Zeynep Ilgin Kolabas ◽  
Louis B. Kuemmerle ◽  
Robert Perneczky ◽  
Benjamin Foerstera ◽  
Maren Buttner ◽  
...  

The meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The calvaria harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins. Acute brain injury induces skull-specific alterations including increased calvaria cell numbers. Moreover, TSPO-positron-emission-tomography imaging of stroke, multiple sclerosis and neurodegenerative disease patients demonstrate disease-associated uptake patterns in the human skull, mirroring the underlying brain inflammation. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260374
Author(s):  
Shiyao Guo ◽  
Yuxia Sheng ◽  
Li Chai ◽  
Jingxin Zhang

Low count PET (positron emission tomography) imaging is often desirable in clinical diagnosis and biomedical research, but its images are generally very noisy, due to the very weak signals in the sinograms used in image reconstruction. To address this issue, this paper presents a novel kernel graph filtering method for dynamic PET sinogram denoising. This method is derived from treating the dynamic sinograms as the signals on a graph, and learning the graph adaptively from the kernel principal components of the sinograms to construct a lowpass kernel graph spectrum filter. The kernel graph filter thus obtained is then used to filter the original sinogram time frames to obtain the denoised sinograms for PET image reconstruction. Extensive tests and comparisons on the simulated and real life in-vivo dynamic PET datasets show that the proposed method outperforms the existing methods in sinogram denoising and image enhancement of dynamic PET at all count levels, especially at low count, with a great potential in real life applications of dynamic PET imaging.


Author(s):  
Naeem-Ul-Haq Khan ◽  
Alicia Corlett ◽  
Craig A. Hutton ◽  
Mohammad B. Haskali

AbstractMany cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other lung carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization and quantification of this receptor in vivo using positron emission tomography imaging. CP04 1 and MG11 2 are two previously described truncated peptides derived from the native CCK-2R hormone ligand, gastrin. The N-terminus of the MG11 2 octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) and aliphatic (2-fluoropropionate) moieties. To assess the impact these modifications had on CCK-2R binding, ligand-binding assays were conducted using A431 cells overexpressing human CCK-2R. MG11 2 modified by 4-fluorobenzoate (FB-MG11 3) demonstrated the highest binding affinity (0.20 nM) followed by MG11 2 modified by 6-fluoronicotinate (FNic-MG11 4; 0.74 nM) and 2-fluoropropionate (FP-MG11 5; 1.80 nM), respectively. Whilst indirect labelling of MG11 2 using fluorine-18 labelled activated esters of fluorobenzoate and 6-fluoronicotinate was unsuccessful, direct fluorine-18 labelling at the N-terminus modified with 6-nitronicotinate afforded a 47.6% radiochemical yield of [18F]FNic-MG11. Unfortunately, [18F]FNic-MG11 4 was chemically unstable, decomposing slowly through defluorination, thereby impeding any further work with this radiotracer.


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