scholarly journals Mapping nephron mass in vivo using positron emission tomography

2020 ◽  
Author(s):  
Edwin J. Baldelomar ◽  
David Reichert ◽  
Kooresh I. Shoghi ◽  
Scott C Beeman ◽  
Jennifer R. Charlton ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Standardized Uptake Value ◽  
Human Kidney ◽  
Clinical Translation ◽  
Emission Tomography ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
The Difference ◽  
Increased Susceptibility

Nephron number varies widely in humans. A low nephron endowment at birth or a loss of functioning nephrons is strongly linked to increased susceptibility to chronic kidney disease. In this work, we develop a contrast agent, RadioCF, to map functioning glomeruli in vivo in the kidney using positron emission tomography (PET). PET radiotracers can be detected in trace doses (<30 nmol), making them useful for rapid clinical translation. RadioCF is formed from cationic ferritin (CF) and with a radioisotope, Cu-64, incorporated into the ferritin core. We show that RadioCF binds specifically to kidney glomeruli after intravenous injection in mice, while radiolabeled non-cationic ferritin, (RadioNF), and free Cu-64 do not. We then show that RadioCF-PET can distinguish kidneys in healthy wild type (WT) mice from kidneys in mice with oligosyndactylism (Os/+), a model of congenital hypoplasia and low nephron mass. Average standardized uptake value (SUV) measured by PET 90 minutes after injection was 21% higher in WT mice than in Os/+ mice, consistent with the higher glomerular density in WT mice. The difference in peak SUV from SUV at 90 minutes correlated with glomerular density in male mice from both WT and Os/+ cohorts (R2 = 0.98). Finally, we used RadioCF-PET to map functioning glomeruli in a donated human kidney. SUV within the kidney correlated with glomerular number (R2= 0.78) measured CF-enhanced magnetic resonance imaging in the same locations. This work suggests that RadioCF-PET appears to accurately detect nephron mass and has the potential for clinical translation.

scholarly journals Evaluation of Skeletal Muscle Activity During Foot Training Exercises Using Positron Emission Tomography

2021 ◽  
Author(s):  
Tomoyuki Kanayama ◽  
Junsuke Nakase ◽  
Takafumi Mochizuki ◽  
Kazuki Asai ◽  
Rikuto Yoshimizu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Positron Emission Tomography ◽  
Muscle Activity ◽  
Skeletal Muscles ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Abductor Hallucis ◽  
Continuous Training ◽  
Positron Emission ◽  
The Difference

Abstract The foot exercises “rock-paper-scissors” and “towel gathering” are widely used in patients with lower limb disorders; however, there are no detailed reports on muscle activity during such training. We quantitatively evaluated the difference in skeletal muscle activity between the two exercises using positron emission tomography. Eight university student athletes were included. Four participants each were assigned to the foot rock-paper-scissors and towel gathering groups. Participants in each group underwent continuous training for 15 min. They received an intravenous injection of 18F-fluorodeoxyglucose and retrained for 15 min, following which they rested for 45 min. Regions of interest were defined in 25 muscles. The standardized uptake value (SUV) in the trained limb was compared with that in the non-trained control limb. SUVs increased in four skeletal muscles (tibialis anterior, peroneus brevis, extensor hallucis brevis, and abductor hallucis) in the rock-paper-scissors group, and in four muscles (flexor digitorum longus, extensor hallucis brevis, extensor digitorum brevis, and quadratus plantae) in the towel gathering group. Thus, foot rock-paper-scissors and towel gathering affected skeletal muscles related to the medial longitudinal arch and toe grip strength, respectively. Given that the two exercises target different skeletal muscles, they should be taught and implemented according to their respective purposes.

scholarly journals Radiosynthesis and Biological Investigation of a Novel Fluorine-18 Labeled Benzoimidazotriazine- Based Radioligand for the Imaging of Phosphodiesterase 2A with Positron Emission Tomography

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4149
Author(s):  
Ritawidya ◽  
Wenzel ◽  
Teodoro ◽  
Toussaint ◽  
Kranz ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Binding ◽  
Standardized Uptake Value ◽  
Radiochemical Yield ◽  
Biological Evaluation ◽  
Emission Tomography ◽  
Biological Investigation ◽  
Positron Emission

A specific radioligand for the imaging of cyclic nucleotide phosphodiesterase 2A (PDE2A) via positron emission tomography (PET) would be helpful for research on the physiology and disease-related changes in the expression of this enzyme in the brain. In this report, the radiosynthesis of a novel PDE2A radioligand and the subsequent biological evaluation were described. Our prospective compound 1-(2-chloro-5-methoxy phenyl)-8-(2-fluoropyridin-4-yl)-3- methylbenzo[e]imidazo[5,1-c][1,2,4]triazine, benzoimidazotriazine (BIT1) (IC50 PDE2A = 3.33 nM; 16-fold selectivity over PDE10A) was fluorine-18 labeled via aromatic nucleophilic substitution of the corresponding nitro precursor using the K[18F]F‐K2.2.2‐carbonate complex system. The new radioligand [18F]BIT1 was obtained with a high radiochemical yield (54 ± 2%, n = 3), a high radiochemical purity (≥99%), and high molar activities (155–175 GBq/μmol, n = 3). In vitro autoradiography on pig brain cryosections exhibited a heterogeneous spatial distribution of [18F]BIT1 corresponding to the known pattern of expression of PDE2A. The investigation of in vivo metabolism of [18F]BIT1 in a mouse revealed sufficient metabolic stability. PET studies in mouse exhibited a moderate brain uptake of [18F]BIT1 with a maximum standardized uptake value of ~0.7 at 5 minutes p.i. However, in vivo blocking studies revealed a non-target specific binding of [18F]BIT1. Therefore, further structural modifications are needed to improve target selectivity.

Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe

Stroke ◽  
2021 ◽  
Author(s):  
David Izquierdo-Garcia ◽  
Himashinie Diyabalanage ◽  
Ian A. Ramsay ◽  
Nicholas J. Rotile ◽  
Adam Mauskapf ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Risk ◽  
Ex Vivo ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Back Muscle ◽  
Plaque Disruption ◽  
Positron Emission ◽  
Human Carotid

Background and Purpose: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. Methods: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68 Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68 Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value. Results: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group ( P <0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68 Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68 Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe. Conclusions: We demonstrated that molecular fibrin PET imaging using 68 Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68 Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.

Season of Birth and Vulnerability to the Pathology of Alzheimer’s Disease: an in Vivo Positron Emission Tomography Study

2021 ◽  
Author(s):  
Fumihiko Yasuno ◽  
Hiroyuki Minami
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Analysis Of Covariance ◽  
Emission Tomography ◽  
Disease Assessment ◽  
Positron Emission

Abstract This study used positron emission tomography to examine whether the seasonal birth effect as an exogenic indicator of early life environmental factors influenced vulnerability to Alzheimer’s disease (AD) pathology in the elderly. We analyzed datasets from the Alzheimer’s Disease Neuroimaging Initiative, which included the data for 234 cognitively normal individuals and patients with mild cognitive impairment (n = 115) and AD dementia (n = 38). As an index of amyloid β (Aβ)/tau accumulation, the AV-45/AV-1451-standardized uptake value ratios (SUVRs) were compared between groups of spring-to-summer births and fall-to-winter births by analysis of covariance. Seasonal birth difference was a good predictor of AV-1451 SUVR. We found that participants with a fall-to-winter birth showed lower AV-1451 SUVRs than those with a spring-to-summer birth, after accounting for the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS) score and other factors that could possibly affect tau accumulation. Our findings showed a vulnerability to tau pathology in participants with a fall-to-winter birth, which may be caused by perinatal or postnatal brain damage due to the risk factors associated with the cold season.

scholarly journals Tumor Metabolism and Blood Flow Changes by Positron Emission Tomography: Relation to Survival in Patients Treated With Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer

2008 ◽  
Vol 26 (27) ◽  
pp. 4449-4457 ◽  
Author(s):  
Lisa K. Dunnwald ◽  
Julie R. Gralow ◽  
Georgiana K. Ellis ◽  
Robert B. Livingston ◽  
Hannah M. Linden ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Standardized Uptake Value ◽  
Advanced Breast ◽  
Emission Tomography ◽  
Mortality Risks ◽  
Positron Emission

Purpose Patients with locally advanced breast carcinoma (LABC) receive preoperative chemotherapy to provide early systemic treatment and assess in vivo tumor response. Serial positron emission tomography (PET) has been shown to predict pathologic response in this setting. We evaluated serial quantitative PET tumor blood flow (BF) and metabolism as in vivo measurements to predict patient outcome. Patients and Methods Fifty-three women with primary LABC underwent dynamic [18F]fluorodeoxyglucose (FDG) and [15O]water PET scans before and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and transport (FDG K1) parameters were calculated; BF was estimated from the [15O]water study. Associations between BF, MRFDG, FDG K1, and standardized uptake value and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results Patients with persistent or elevated BF and FDG K1 from baseline to midtherapy had higher recurrence and mortality risks than patients with reductions. In multivariable analyses, BF and FDG K1 changes remained independent prognosticators of DFS and OS. For example, in the association between BF and mortality, a patient with a 5% increase in tumor BF had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001). Conclusion LABC patients with limited or no decline in BF and FDG K1 experienced higher recurrence and mortality risks that were greater than the effects of clinical tumor characteristics. Tumor perfusion changes over the course of neoadjuvant chemotherapy measured directly by [15O]water or indirectly by dynamic FDG predict DFS and OS.

Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system

2020 ◽  
Vol 133 (4) ◽  
pp. 1010-1019 ◽  
Author(s):  
Hiroaki Takei ◽  
Jun Shinoda ◽  
Soko Ikuta ◽  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Who Classification ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
World Health ◽  
Pet Tracers ◽  
Positron Emission ◽  
Significant Difference ◽  
The Mean

OBJECTIVEPositron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification.METHODSIn total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers.RESULTSThere were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG.CONCLUSIONSPET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

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