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 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 Current Perspectives on 89Zr-PET Imaging

2020 ◽  
Vol 21 (12) ◽  
pp. 4309
Author(s):  
Joon-Kee Yoon ◽  
Bok-Nam Park ◽  
Eun-Kyoung Ryu ◽  
Young-Sil An ◽  
Su-Jin Lee
Keyword(s):  
Pet Imaging ◽  
Cell Tracking ◽  
Current Status ◽  
Cancer Therapies ◽  
Ongoing Research ◽  
Positron Emission ◽  
Nanoparticle Imaging ◽  
Anti Cancer ◽  
Preclinical And Clinical Studies

89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 days) is favorable for evaluating the in vivo distribution of monoclonal antibodies. Thus, the use of 89Zr is promising for monitoring antibody-based cancer therapies. Immuno-PET combines the sensitivity of PET with the specificity of antibodies. A number of studies have been conducted to investigate the feasibility of 89Zr immuno-PET imaging for predicting the efficacy of radioimmunotherapy and antibody therapies, imaging target expression, detecting target-expressing tumors, and the monitoring of anti-cancer chemotherapies. In this review, we summarize the current status of PET imaging using 89Zr in both preclinical and clinical studies by highlighting the use of immuno-PET for the targets of high clinical relevance. We also present 89Zr-PET applications other than immuno-PET, such as nanoparticle imaging and cell tracking. Finally, we discuss the limitations and the ongoing research being performed to overcome the remaining hurdles.

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 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.

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.

scholarly journals Rare Intensely Fluorine-18-fluorodeoxyglucose Avid Large Retropharyngeal Goiter in a Patient with Invasive Breast Carcinoma

2016 ◽  
Vol 6 ◽  
pp. 13
Author(s):  
Bina Kviatkovsky ◽  
Elliot Landau ◽  
Muhammad Siddique ◽  
Arnold Brenner
Keyword(s):  
Breast Cancer ◽  
Standardized Uptake Value ◽  
Retropharyngeal Space ◽  
Breast Cancer Patients ◽  
Chronic Thyroiditis ◽  
Invasive Ductal Breast Cancer ◽  
Positron Emission ◽  
Pet Scans ◽  
Fluorine 18 Fluorodeoxyglucose ◽  
Fdg Avidity

Diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) avidity on positron emission tomography (PET) scans has been demonstrated in patients with chronic thyroiditis, likely secondary to increased inflammatory cell glucose uptake. A complex association has been demonstrated between breast cancer and thyroid disease, although the mechanism remains elusive. Development of chronic thyroiditis and/or goiter in breast cancer patients has been suggested to convey a more favorable prognosis. Goiter extension is almost exclusively into retrosternal space, with only a handful of cases reported with superior extension into retropharyngeal space. We present a rare case of a diffusely enlarged goiter extending superior and posterior into the retropharyngeal space with an associated intense 18F-FDG avidity standardized uptake value maximum (SUVmax) of 16.1 in a patient with invasive ductal breast cancer. To our knowledge, this represents the first published case of diffusely 18F-FDG avid goiter with retropharyngeal extension.

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.

ANTICANCER EFFECT OF UVARIA GENUS

2014 ◽  
pp. 98-101
Author(s):  
Thi Bich Hien Le ◽  
Viet Duc Ho ◽  
Thi Hoai Nguyen
Keyword(s):  
Biological Activities ◽  
Current Trend ◽  
Healthcare Systems ◽  
Chemical Compositions ◽  
Cancer Therapies ◽  
Pharmacological Effects ◽  
Anticancer Effect ◽  
Anti Cancer ◽  
Tropical Areas ◽  
Cancer Activity

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.

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