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Article ; Online: PET Imaging of Active Invasive Fungal Infections with d-[5-

Co, Cynthia M / Mulgaonkar, Aditi / Zhou, Ning / Harris, Shelby / Öz, Orhan K / Tang, Liping / Sun, Xiankai

ACS infectious diseases

2022 Volume 8, Issue 8, Page(s) 1663–1673

Abstract: ... from d-amino acids (DAAs) show promise as bacterial-specific positron emission tomography (PET) imaging ... mammals, fungi can utilize external DAAs including d-glutamine for their growth by rapidly upregulating ... virulence. We previously validated d-[5- ...

Abstract	The increasing prevalence and severity of invasive fungal infections (IFIs), especially in immunocompromised populations, has amplified the need for rapid diagnosis of fungal pathogens. Radiotracers derived from d-amino acids (DAAs) show promise as bacterial-specific positron emission tomography (PET) imaging agents due to their preferential consumption by bacteria and largely nonutilization by hosts. Unlike mammals, fungi can utilize external DAAs including d-glutamine for their growth by rapidly upregulating DAA oxidases. Additionally, glutamine is essential for fungal nitrogen assimilation, survival, and virulence. We previously validated d-[5-
MeSH term(s)	Animals ; Candida albicans ; Glutamine/chemistry ; Invasive Fungal Infections ; Mammals ; Mice ; Mycoses ; Positron-Emission Tomography
Chemical Substances	Glutamine (0RH81L854J)
Language	English
Publishing date	2022-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.2c00249
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Article: Difficult diagnosis and localization of focal nesidioblastosis: clinical implications of (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning.

Kim, Jae Ri / Jang, Jin-Young / Shin, Yong Chan / Cho, Young Min / Kim, Hongbeom / Kwon, Wooil / Han, Young Min / Kim, Sun-Whe

Annals of surgical treatment and research

2016 Volume 91, Issue 1, Page(s) 51–55

Abstract: ... for biliary-pancreatic surgeons. (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning and (111)indium ...

Abstract	Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning and (111)indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results.
Language	English
Publishing date	2016-06-30
Publishing country	Korea (South)
Document type	Case Reports
ZDB-ID	3012234-X
ISSN	2288-6796 ; 2288-6575
ISSN (online)	2288-6796
ISSN	2288-6575
DOI	10.4174/astr.2016.91.1.51
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Article: Tumor imaging using 1-(2'-deoxy-2'-18F-fluoro-beta-D-arabinofuranosyl)thymine and PET.

Tehrani, Omid S / Muzik, Otto / Heilbrun, Lance K / Douglas, Kirk A / Lawhorn-Crews, Jawana M / Sun, Haihao / Mangner, Thomas J / Shields, Anthony F

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2007 Volume 48, Issue 9, Page(s) 1436–1441

Abstract: Unlabelled: The kinetics of 1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine (FMAU) were ... studied using PET to determine the most appropriate and simplest approach to image acquisition and ... with brain (n = 4) or prostate (n = 6) tumors were imaged using (18)F-FMAU PET (mean dose, 369 MBq). Sixty ...

Abstract	Unlabelled: The kinetics of 1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine (FMAU) were studied using PET to determine the most appropriate and simplest approach to image acquisition and analysis. The concept of tumor retention ratio (TRR) is introduced and validated. Methods: Ten patients with brain (n = 4) or prostate (n = 6) tumors were imaged using (18)F-FMAU PET (mean dose, 369 MBq). Sixty-minute dynamic images were obtained; this was followed by whole-body images. Mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) of each tumor were determined as the mean over 3 planes of each time interval. For kinetic analyses, blood activity was measured in 18 samples over 60 min. Samples were analyzed by high-performance liquid chromatography at 3 selected times to determine tracer metabolites. FMAU kinetics were measured using a 3-compartment model yielding the flux (K1 x k3/(k2 + k3)) (K1, k2, and k3 are rate constants) and compared with TRR measurements. TRR was calculated as the tumor (18)F-FMAU uptake area under the curve divided by the product of blood (18)F-FMAU AUC and time. A similar analysis was performed using muscle to estimate (18)F-FMAU delivery. Results: SUVmean measurements obtained from 5 to 11 min correlated with those obtained from 30 to 60 min (r(2) = 0.92, P < 0.0001) and 50 to 60 min (r(2) = 0.92, P < 0.0001) due to the rapid clearance of (18)F-FMAU. Similar results were obtained using SUVmax measurements (r(2) = 0.93, P < 0.0001; r(2) = 0.88, P < 0.0001, respectively). The measurement of TRR using either blood or muscle activity over 11 min provided results comparable to those of 60-min dynamic imaging and a 3-compartment model. This analysis required only 5 blood samples drawn at 1, 2, 3, 5, and 11 min without metabolite correction to produce comparable results. Conclusion: Tissue retention ratio measurements obtained over 11 min can replace flux measurements in (18)F-FMAU imaging. The SUVmean and the SUVmax in 5-11 min images correlated well with those of images obtained at 50-60 min. The quality of the images and tissue kinetics in 11 min of imaging makes it a desirable and shorter tumor imaging option.
MeSH term(s)	Arabinofuranosyluracil/analogs & derivatives ; Arabinofuranosyluracil/pharmacokinetics ; Brain Neoplasms/diagnostic imaging ; Humans ; Male ; Positron-Emission Tomography/methods ; Prostatic Neoplasms/diagnostic imaging ; Radiopharmaceuticals/pharmacokinetics
Chemical Substances	Radiopharmaceuticals ; Arabinofuranosyluracil (3083-77-0) ; clevudine (IN51MVP5F1)
Language	English
Publishing date	2007-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
DOI	10.2967/jnumed.107.042762
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Article: Biodistribution and radiation dosimetry estimates of 1-(2'-deoxy-2'-(18)F-Fluoro-1-beta-D-arabinofuranosyl)-5-bromouracil: PET imaging studies in dogs.

Nimmagadda, Sridhar / Mangner, Thomas J / Sun, Haihao / Klecker, Raymond W / Muzik, Otto / Lawhorn-Crews, Jawana M / Douglas, Kirk A / Collins, Jerry M / Shields, Anthony F

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2005 Volume 46, Issue 11, Page(s) 1916–1922

Abstract: ... 18)F-fluoro-1-beta-d-arabinofuranosyl)-5-bromouracil ((18)F-FBAU), a potential tracer for imaging DNA ... synthesis.: Methods: Three normal dogs were intravenously administered (18)F-FBAU and a dynamic PET scan ... of the tracer in different organs was derived from reconstructed PET images. The radiation dosimetry of (18)F ...

Abstract	Unlabelled: This study reports on the biodistribution and radiation estimates of 1-(2'-deoxy-2'-(18)F-fluoro-1-beta-d-arabinofuranosyl)-5-bromouracil ((18)F-FBAU), a potential tracer for imaging DNA synthesis. Methods: Three normal dogs were intravenously administered (18)F-FBAU and a dynamic PET scan was performed for 60 min over the upper abdomen followed by a whole-body scan for a total of 150 min. Blood samples were collected at stipulated time intervals to evaluate tracer clearance and metabolism. Tissue samples of various organs were analyzed for tracer uptake and DNA incorporation. Dynamic accumulation of the tracer in different organs was derived from reconstructed PET images. The radiation dosimetry of (18)F-FBAU was evaluated using the MIRD method. Results: At 60 min after injection, blood analysis found >90% of the activity in unmetabolized form. At 2 h after injection, (18)F-FBAU uptake was highest in proliferating tissues (mean SUVs: marrow, 2.6; small intestine, 4.0), whereas nonproliferative tissues showed little uptake (mean SUVs: muscle, 0.75; lung, 0.70; heart, 0.85; liver, 1.28). Dynamic image analysis over 60 min showed progressive uptake of the tracer in marrow. Extraction studies demonstrated that most of the activity in proliferative tissues was in the acid-insoluble fraction (marrow, 83%; small intestine, 73%), consistent with incorporation into DNA. In nonproliferative tissue, most of the activity was not found in the acid-insoluble fraction (>84% for heart, muscle, and liver). Conclusion: These results demonstrate that (18)F-FBAU was resistant to metabolism, readily incorporated into DNA in proliferating tissues, and showed good contrast between organs of variable DNA synthesis. These findings indicate that (18)F-FBAU may find use in measuring DNA synthesis with PET.
MeSH term(s)	Animals ; Body Burden ; Bromouracil/analogs & derivatives ; Bromouracil/pharmacokinetics ; Cell Line, Tumor ; Dogs ; Humans ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Organ Specificity ; Positron-Emission Tomography/methods ; Radiation Dosage ; Radiometry ; Radiopharmaceuticals/pharmacokinetics ; Relative Biological Effectiveness ; Tissue Distribution ; Whole Body Imaging ; Whole-Body Counting
Chemical Substances	1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil ; Radiopharmaceuticals ; Bromouracil (4HK400G5UO)
Language	English
Publishing date	2005-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: A systems identification approach using Bayes factors to deconstruct the brain bases of emotion regulation.

Bo, Ke / Kraynak, Thomas E / Kwon, Mijin / Sun, Michael / Gianaros, Peter J / Wager, Tor D

Nature neuroscience

2024

Abstract: Cognitive reappraisal is fundamental to cognitive therapies and everyday emotion regulation. Analyses using Bayes factors and an axiomatic systems identification approach identified four reappraisal-related components encompassing distributed neural ... ...

Abstract	Cognitive reappraisal is fundamental to cognitive therapies and everyday emotion regulation. Analyses using Bayes factors and an axiomatic systems identification approach identified four reappraisal-related components encompassing distributed neural activity patterns across two independent functional magnetic resonance imaging (fMRI) studies (n = 182 and n = 176): (1) an anterior prefrontal system selectively involved in cognitive reappraisal; (2) a fronto-parietal-insular system engaged by both reappraisal and emotion generation, demonstrating a general role in appraisal; (3) a largely subcortical system activated during negative emotion generation but unaffected by reappraisal, including amygdala, hypothalamus and periaqueductal gray; and (4) a posterior cortical system of negative emotion-related regions downregulated by reappraisal. These systems covaried with individual differences in reappraisal success and were differentially related to neurotransmitter binding maps, implicating cannabinoid and serotonin systems in reappraisal. These findings challenge 'limbic'-centric models of reappraisal and provide new systems-level targets for assessing and enhancing emotion regulation.
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-024-01605-7
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

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Article ; Online: T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy.

Sim, Malcolm J W / Sun, Peter D

Frontiers in immunology

2022 Volume 13, Page(s) 833017

Abstract: In cancer, non-synonymous DNA base changes alter protein sequence and produce neoantigens that are detected by the immune system. For immune detection, neoantigens must first be presented on class I or II human leukocyte antigens (HLA) followed by ... ...

Abstract	In cancer, non-synonymous DNA base changes alter protein sequence and produce neoantigens that are detected by the immune system. For immune detection, neoantigens must first be presented on class I or II human leukocyte antigens (HLA) followed by recognition by peptide-specific receptors, exemplified by the T-cell receptor (TCR). Detection of neoantigens represents a unique challenge to the immune system due to their high similarity with endogenous 'self' proteins. Here, we review insights into how TCRs detect neoantigens from structural studies and delineate two broad mechanistic categories: 1) recognition of mutated 'self' peptides and 2) recognition of novel 'non-self' peptides generated through anchor residue modifications. While mutated 'self' peptides differ only by a single amino acid from an existing 'self' epitope, mutations that form anchor residues generate an entirely new epitope, hitherto unknown to the immune system. We review recent structural studies that highlight these structurally distinct mechanisms and discuss how they may lead to differential anti-tumor immune responses. We discuss how T cells specific for neoantigens derived from anchor mutations can be of high affinity and provide insights to their use in adoptive T cell transfer-based immunotherapy.
MeSH term(s)	Antigens, Neoplasm ; Epitopes ; Humans ; Immunologic Factors ; Immunotherapy ; Neoplasms/genetics ; Neoplasms/therapy ; Peptides ; Receptors, Antigen, T-Cell ; T-Lymphocytes
Chemical Substances	Antigens, Neoplasm ; Epitopes ; Immunologic Factors ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2022-02-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.833017
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Article: High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.

Lu, Jinghua / Sun, Peter D

bioRxiv : the preprint server for biology

2020

Abstract: A novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many ... ...

Abstract	A novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides Ang II to control vasodilatation and permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we wonder how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ~3-10 fold when fluorogenic caspase-1 substrate and Bradykinin-analog peptides were used to characterize ACE2 activity. In addition, the enhancement was mediated by ACE2 binding of RBD domain of SARS-CoV-2 spike. These results highlighted the altered activity of ACE2 during SARS-CoV-2 infection and would shed new lights on the pathogenesis of COVID-19 and its complications for better treatments.
Keywords	covid19
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.01.182659
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Article ; Online: High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.

Lu, Jinghua / Sun, Peter D

The Journal of biological chemistry

2020 Volume 295, Issue 52, Page(s) 18579–18588

Abstract: The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ...

Abstract	The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/enzymology ; COVID-19/metabolism ; COVID-19/virology ; Humans ; Protein Binding ; Protein Domains ; Proteolysis ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Surface Plasmon Resonance/methods
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-10-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA120.015303
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Article ; Online: FcγRI FG-loop functions as a pH sensitive switch for IgG binding and release.

Lu, Jinghua / Spencer, Matthew / Zou, Zhongcheng / Traver, Maria / Brzostowski, Joseph / Sun, Peter D

Frontiers in immunology

2023 Volume 14, Page(s) 1100499

Abstract: Understanding the molecular mechanism underlying the hierarchic binding between FcγRs and IgG antibodies is critical for therapeutic antibody engineering and FcγR functions. The recent determination of crystal structures of FcγRI-Fc complexes, however, ... ...

Abstract	Understanding the molecular mechanism underlying the hierarchic binding between FcγRs and IgG antibodies is critical for therapeutic antibody engineering and FcγR functions. The recent determination of crystal structures of FcγRI-Fc complexes, however, resulted in two controversial mechanisms for the high affinity receptor binding to IgG. Here, we describe high resolution structures of a bovine FG-loop variant of FcγRI in complex with the Fc fragment of IgG
MeSH term(s)	Animals ; Cattle ; Receptors, IgG/metabolism ; Immunoglobulin G ; Protein Binding ; Phagocytosis ; Hydrogen-Ion Concentration
Chemical Substances	Receptors, IgG ; Immunoglobulin G
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1100499
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Article: Purinoreceptors and ectonucleotidases control ATP-induced calcium waveforms and calcium-dependent responses in microglia: Roles of P2 receptors and CD39 in ATP-stimulated microglia.

Chun, Byeong J / Aryal, Surya P / Varughese, Peter / Sun, Bin / Bruno, Joshua A / Richards, Chris I / Bachstetter, Adam D / Kekenes-Huskey, Peter M

Frontiers in physiology

2023 Volume 13, Page(s) 1037417

Abstract: Adenosine triphosphate (ATP) and its metabolites drive microglia migration and cytokine production by activating P2X- and P2Y- class purinergic receptors. Purinergic receptor activation gives rise to diverse intracellular calcium (Ca2+ signals, or ... ...

Abstract	Adenosine triphosphate (ATP) and its metabolites drive microglia migration and cytokine production by activating P2X- and P2Y- class purinergic receptors. Purinergic receptor activation gives rise to diverse intracellular calcium (Ca2+ signals, or waveforms, that differ in amplitude, duration, and frequency. Whether and how these characteristics of diverse waveforms influence microglia function is not well-established. We developed a computational model trained with data from published primary murine microglia studies. We simulate how purinoreceptors influence Ca2+ signaling and migration, as well as, how purinoreceptor expression modifies these processes. Our simulation confirmed that P2 receptors encode the amplitude and duration of the ATP-induced Ca2+ waveforms. Our simulations also implicate CD39, an ectonucleotidase that rapidly degrades ATP, as a regulator of purinergic receptor-induced Ca2+ responses. Namely, it was necessary to account for CD39 metabolism of ATP to align the model's predicted purinoreceptor responses with published experimental data. In addition, our modeling results indicate that small Ca2+ transients accompany migration, while large and sustained transients are needed for cytokine responses. Lastly, as a proof-of-principal, we predict Ca2+ transients and cell membrane displacements in a BV2 microglia cell line using published P2 receptor mRNA data to illustrate how our computer model may be extrapolated to other microglia subtypes. These findings provide important insights into how differences in purinergic receptor expression influence microglial responses to ATP.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.1037417
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