scholarly journals Characterization of 18F-PM-PBB3 (18F-APN-1607) Uptake in the rTg4510 Mouse Model of Tauopathy

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1750 ◽  
Author(s):  
Chi-Chang Weng ◽  
Ing-Tsung Hsiao ◽  
Qing-Fang Yang ◽  
Cheng-Hsiang Yao ◽  
Chin-Yin Tai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ex Vivo ◽  
Standardized Uptake Value ◽  
Dynamic Imaging ◽  
Scanning Time ◽  
Positron Emission ◽  
Image Characteristics ◽  
Uptake Pattern ◽  
Pet Scans

Misfolding, aggregation, and cerebral accumulation of tau deposits are hallmark features of Alzheimer’s disease. Positron emission tomography study of tau can facilitate the development of anti-tau treatment. Here, we investigated a novel tau tracer 18F-PM-PBB3 (18F-APN-1607) in a mouse model of tauopathy. Dynamic PET scans were collected in groups of rTg4510 transgenic mice at 2–11 months of age. Associations between distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) with cerebellum reference were used to determine the optimal scanning time and uptake pattern for each age. Immunohistochemistry staining of neurofibrillary tangles and autoradiography study was performed for ex vivo validation. An SUVR 40–70 min was most consistently correlated with DVR and was used in further analyses. Significant increased 18F-PM-PBB3 uptake in the brain cortex was found in six-month-old mice (+28.9%, p < 0.05), and increased further in the nine-month-old group (+38.8%, p < 0.01). The trend of increased SUVR value remained evident in the hippocampus and striatum regions except for cortex where uptake becomes slightly reduced in 11-month-old animals (+37.3%, p < 0.05). Radioactivity distributions from autoradiography correlate well to the presence of human tau (HT7 antibody) and hyperphosphorylated tau (antibody AT8) from the immunohistochemistry study of the adjacent brain sections. These findings supported that the 40–70 min 18F-PM-PBB3 PET scan with SUVR measurement can detect significantly increased tau deposits in a living rTg4510 transgenic mouse models as early as six-months-old. The result exhibited promising dynamic imaging capability of this novel tau tracer, and the above image characteristics should be considered in the design of longitudinal preclinical tau image studies.

scholarly journals Repeatability of parametric methods for [18F]florbetapir imaging in Alzheimer’s disease and healthy controls: A test–retest study

2020 ◽  
pp. 0271678X2091540 ◽  
Author(s):  
Sander CJ Verfaillie ◽  
Sandeep SV Golla ◽  
Tessa Timmers ◽  
Hayel Tuncel ◽  
Chris WJ van der Weijden ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Parametric Methods ◽  
Excellent Performance ◽  
Reference Tissue ◽  
Positron Emission ◽  
Arterial Sampling ◽  
Pet Scans

Accumulation of amyloid beta (Aβ) is one of the pathological hallmarks of Alzheimer’s disease (AD), which can be visualized using [18F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [18F]florbetapir PET scans, including arterial sampling, were acquired ( n = 8 AD patient, n = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUVr(50–70)). BPND+1, DVR, VT and SUVr were compared with corresponding estimates (VT or DVR) from the plasma input reversible two tissue compartmental (2T4k_VB) model with corresponding TRT values for 90-scan duration. RPM ( r2 = 0.92; slope = 0.91), Logan ( r2 = 0.95; slope = 0.84) and rLogan ( r2 = 0.94; slope = 0.88), and SRTM2 ( r2 = 0.91; slope = 0.83), SA ( r2 = 0.91; slope = 0.88), SUVr ( r2 = 0.84; slope = 1.16) correlated well with their 2T4k_VB counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUVr(50–70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [18F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.

scholarly journals Characterization of an Orthotopic Colorectal Cancer Mouse Model and Its Feasibility for Accurate Quantification in Positron Emission Tomography

2017 ◽  
Vol 19 (5) ◽  
pp. 762-771 ◽  
Author(s):  
Sara Rapic ◽  
Christel Vangestel ◽  
Jeroen Verhaeghe ◽  
Tim Van den Wyngaert ◽  
Rukun Hinz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Positron Emission Tomography ◽  
Mouse Model ◽  
Emission Tomography ◽  
Positron Emission ◽  
Accurate Quantification

scholarly journals Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8245
Author(s):  
Thomas Wanek ◽  
Viktoria Zoufal ◽  
Mirjam Brackhan ◽  
Markus Krohn ◽  
Severin Mairinger ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Slices ◽  
Immunohistochemical Analysis ◽  
Mouse Strains ◽  
Brain Distribution ◽  
Cancer Resistance ◽  
Wild Type ◽  
Positron Emission ◽  
Pet Scans ◽  
The Brain

Background: ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) are co-localized at the blood-brain barrier (BBB), where they restrict the brain distribution of many different drugs. Moreover, ABCB1 and possibly ABCG2 play a role in Alzheimer’s disease (AD) by mediating the brain clearance of beta-amyloid (Aβ) across the BBB. This study aimed to compare the abundance and activity of ABCG2 in a commonly used β-amyloidosis mouse model (APP/PS1-21) with age-matched wild-type mice. Methods: The abundance of ABCG2 was assessed by semi-quantitative immunohistochemical analysis of brain slices of APP/PS1-21 and wild-type mice aged 6 months. Moreover, the brain distribution of two dual ABCB1/ABCG2 substrate radiotracers ([11C]tariquidar and [11C]erlotinib) was assessed in APP/PS1-21 and wild-type mice with positron emission tomography (PET). [11C]Tariquidar PET scans were performed without and with partial inhibition of ABCG2 with Ko143, while [11C]erlotinib PET scans were only performed under baseline conditions. Results: Immunohistochemical analysis revealed a significant reduction (by 29–37%) in the number of ABCG2-stained microvessels in the brains of APP/PS1-21 mice. Partial ABCG2 inhibition significantly increased the brain distribution of [11C]tariquidar in APP/PS1-21 and wild-type mice, but the brain distribution of [11C]tariquidar did not differ under both conditions between the two mouse strains. Similar results were obtained with [11C]erlotinib. Conclusions: Despite a reduction in the abundance of cerebral ABCG2 and ABCB1 in APP/PS1-21 mice, the brain distribution of two dual ABCB1/ABCG2 substrates was unaltered. Our results suggest that the brain distribution of clinically used ABCB1/ABCG2 substrate drugs may not differ between AD patients and healthy people.

scholarly journals Evaluation of Integrin αvβ3 Expression in Murine Xenograft Models: [68Ga]Ga-DOTA-C(RGDfK) PET Study with Immunohistochemical Confirmation

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1295
Author(s):  
Kosuke Mitsuyuki ◽  
Tadashi Watabe ◽  
Sadahiro Naka ◽  
Yuwei Liu ◽  
Mitsuaki Tatsumi ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Immunohistochemical Analysis ◽  
Integrin Αvβ3 ◽  
Mouse Tumor ◽  
Cancer Therapies ◽  
Positron Emission ◽  
Anti Cancer ◽  
Potential Applicability ◽  
Xenograft Models ◽  
Pet Scans

Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin αvβ3 expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin αvβ3 in mouse tumor models using [68Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 (n = 6 each). The [68Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin αVβ3 antibody. [68Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin αVβ3 expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin αvβ3 can be differentiated by the [68Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF.

scholarly journals Dynamic PET/CT with the Hepatobiliary Tracer [68Ga]Ga-Tmos-DAZA for Characterization of a Hepatic Tumor

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 660
Author(s):  
Martin Freesmeyer ◽  
Julia Greiser ◽  
Thomas Winkens ◽  
Falk Gühne ◽  
Christian Kühnel ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Liver Perfusion ◽  
Dynamic Imaging ◽  
High Temporal Resolution ◽  
Hepatobiliary Scintigraphy ◽  
Imaging Characteristics ◽  
Positron Emission ◽  
Pet Ct

Established imaging modalities for the characterization of liver tumors are computed tomography (CT), magnetical resonance (MR) imaging, sonography, and hepatobiliary scintigraphy. In some cases, their results may be inconclusive or certain examinations not possible due to contraindications. Positron emission tomography (PET)/CT has the capability of dynamic imaging with high temporal resolution. With radiolabeled tri-alkoxysalicyl-1,4-diazepan-6-amine (TAoS-DAZA) tracers, imaging of liver perfusion and hepatobiliary function is possible in a single examination. In the presented case, the PET/CT was performed in a patient with suspected hepatocellular carcinoma and atypical CT findings. PET imaging characteristics were consistent with a hepatocellular carcinoma (HCC). PET with DAZA ligands may be a supplemental method for liver tumor characterization in difficult cases.

scholarly journals Medial temporal tau can be a predictor for amyloid-ß positivity in mild cognitive impairment

2020 ◽  
Author(s):  
Hanna Cho ◽  
Min Seok Baek ◽  
Hye Sun Lee ◽  
Jae Yong Choi ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Standardized Uptake Value ◽  
Visual Assessment ◽  
Parahippocampal Cortex ◽  
Positron Emission ◽  
Auc Value ◽  
Tau Pet ◽  
Sensitivity Specificity ◽  
Post Hoc ◽  
Pet Scans

Abstract Introduction Although both amyloid-ß (Aß) and tau positron emission tomography (PET) are important for the assessment of Alzheimer’s disease pathology, obtaining two PET scans can be challenging in clinical practice. We sought to determine whether Aß-positivity in MCI patients can be predicted with only a single tau PET scan. Methods We prospectively recruited 105 MCI patients and performed two PET scans with 18 F-florbetaben and 18 F-flortaucipir with all patients. Regional 18 F-flortaucipir standardized uptake value ratios (SUVR) were measured using FreeSurfer-generated volumes-of-interest and with the cerebellar crus median as a reference. Results We classified 49 (46.7%) MCI patients as Aß-positive using visual assessment. In 12 regions showing greater tau uptake in the MCI-Aβ+ patients compared to the MCI-Aβ- patients, tau uptake in the entorhinal cortex showed the greatest area under the curve (AUC) value (AUC = 0.835, sensitivity/specificity = 73.5% /85.7%) for discriminating Aß-positivity. The second and third largest AUCs were obtained with tau uptake in the amygdala (AUC = 0.814, sensitivity/specificity = 65.3%/94.6%) and the parahippocampal cortex (AUC = 0.802, sensitivity/specificity = 67.4%/91.1%). However, post-hoc analyses revealed no statistical differences between the three regions. Conclusions Single tau PET scans may be helpful in the evaluation of disease state and stage at the same time in MCI patients.

Clinical, Radiographic, and Biomarker Characterization of Multiple Myeloma Patients with Bisphosphonate Associated Osteonecrosis of the Jaw.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3591-3591
Author(s):  
Noopur Raje ◽  
Sook-Bin Woo ◽  
Karen Hande ◽  
Jeffrey T. Yap ◽  
Paul G. Richardson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Glucose Metabolism ◽  
Bone Turnover ◽  
Fdg Pet ◽  
Mononuclear Cells ◽  
Standardized Uptake Value ◽  
Osteonecrosis Of The Jaw ◽  
Multiple Imaging ◽  
Pet Scans

Abstract Osteonecrosis of the jaw (ONJ) is a recently described entity observed in patients with a history of aminobisphosphonate use. To date nearly 400 patients with ONJ have been reported in literature and this number continues to rise. However,prospective characterization of ONJ is lacking. We here characterize ONJ clinically and radiographically using multiple imaging modalities including panorex films, CAT scans, magnetic resonance imaging (MRI), FDG-PET scans, and NaF-PET bone scans in 11 patients with multiple myeloma (MM). Moreover, bone turnover and remodelling markers in these patients were analyzed prospectively in order to gain insights into the pathophysiology of ONJ. Eleven patients between the ages of 57 and 81 yrs were included. There were 8 men and 3 women, and 6 patients presented with Durie Salmon stage III disease. Patients were treated with various combinations of conventional and novel agents, including stem cell transplantation (4/11). Patients received either pamidronate (n=3), zolendronic acid (n=4), or both agents sequentially (n=4). The mean duration of bisphosphonate (BP) therapy was 38.7 months (range: 9–81 months). All patients were examined independently by 2 oral medicine physicians, and clinical data was validated on 2 separate dental visits. Six of 11 patients had mandibular lesions, 3 had lesions in the maxilla, and 2/11 patients had lesions in both the maxilla and mandible. Plain and panorex filmsdemonstrated a mottled appearance with increased radiolucency at the site of ONJ.This was associated with an increase in both glucose metabolism and mineralization at sites of ONJ, as measured with the maximum standardized uptake value (SUVmax) on FDG and NaF-PET scans, respectively. However, one patient with increased uptake on NaF-PET did not have increased glucose metabolism with FDG-PET. The target-to-background ratio of SUVmax for NaF-PET scans was significantly greater than FDG-PET suggesting that NaF-PET may have greater sensitivity than FDG-PET in confirming a diagnosis of ONJ. Several markers of bone turnover and remodelling were measured including serum calcium, vitamin D (25-OH), urinary N telopeptides, bone alkaline phosphatase (BAP), osteopontin, MIP 1a, RANK-L, osteoprotegrin, and DKK. Transcriptional profiling on peripheral blood mononuclear cells (PBMCs) using the Affymetrix U133Plus 2.0 gene chip was also performed in all 11 patients and compared with those of 10 MM patients on BP therapy without ONJ and 5 normal donors. These correlative studies will be presented and provide insights into the pathophysiology of ONJ. Importantly these studies both define clinical and radiographic features on ONJ, but also identify biomarkers to be evaluated in future prospective studies of BP therapy and ONJ.

scholarly journals Baseline SUVmax did not predict histological transformation in follicular lymphoma in the phase 3 GALLIUM study

Blood ◽  
2020 ◽  
Vol 135 (15) ◽  
pp. 1214-1218 ◽  
Author(s):  
Farheen Mir ◽  
Sally F. Barrington ◽  
Helen Brown ◽  
Tina Nielsen ◽  
Deniz Sahin ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Standardized Uptake Value ◽  
Tumor Burden ◽  
Phase 3 ◽  
High Tumor Burden ◽  
Positron Emission ◽  
Histological Transformation ◽  
The Difference ◽  
The Relationship ◽  
Pet Scans

Abstract A minority of patients with follicular lymphoma (FL) undergo histological transformation (HT). This retrospective analysis of 549 patients from the phase 3 GALLIUM study (NCT01332968) assessed the relationship between maximum standardized uptake value (SUVmax) at baseline on positron emission tomography (PET) and HT risk. Previously untreated patients with high tumor burden grade 1-3a FL received obinutuzumab- or rituximab-based chemotherapy induction. The relationship between baseline SUVmax (bSUVmax) and HT risk was assessed using cutoff values for SUVmax &gt;10 and &gt;20. Overall, 15 of 549 (2.7%) patients with baseline PET scans experienced biopsy-confirmed HT (median follow-up, 59 months). More than 65% of patients had bSUVmax &gt; 10, with 3.3% of these experiencing HT. Only 1 of 74 (1.4%) patients with bSUVmax &gt; 20 underwent HT. Median bSUVmax in patients with HT vs without HT was 12.4 (range, 8.1-28.0) vs 11.8 (range, 3.1-64.4), respectively; median bSUVrange (the difference between bSUVmax of the most and least 18F-fluorodeoxyglucose–avid lymphoma sites) was 8.0 (range, 1.1-23.9) vs 7.1 (range, 0.0-59.8), respectively. There was no temporal relationship between bSUVmax and HT. Neither bSUVmax nor bSUVrange predicted HT in GALLIUM, suggesting that there may be little benefit in rebiopsy of lesions to exclude HT based on SUVmax alone before initiating therapy in patients with high tumor burden FL.

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