In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized13C-Pyruvate MR Spectroscopy and18F-FDG PET/CT Imaging in a Mouse Model

Objective: While venous thrombosis (VT)-induced inflammation facilitates thrombus resolution, inflammation causes vein wall scarring (VWS). Recently, statins have shown to improve VT resolution and reduce VT inflammatory components. In this study, we hypothesized that early VT inflammation detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) could predict subsequent late stage VWS, and would be attenuated by statin therapy. Methods: Stasis VT was induced in 8-12 week old male C57BL/6 mice (n=31) in either the right jugular vein (n=13) or inferior vena cava (IVC,n=18). Animals in the IVC VT cohort were randomized to statin (n=8) or control (n=10) treatment. Statin, rosuvastatin (5mg/kg), was administered by oral gavage, daily starting 24 hours prior to VT induction; control mice received saline. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG inflammation signals (standard uptake value=SUV) were measured in the thrombosed vein and compared to the sham-operated venous segments or treatment control. On day 14, mice were sacrificed and VT tissue was resected. Picrosirius red staining allowed measurement of collagen and vein wall thickness in VT sections. Results: FDG-PET/CT at day 2 revealed increased inflammation signal activity in jugular VT (SUV 1.43 ± 0.3 VT vs. 0.81 ± 0.3 contralateral vein, p<0.0001). Statin-treated mice showed a trend of decreased inflammation signal at day 2 in the IVC VT models (SUV 1.02 ± 0.1 statin VT vs. 1.42 ± 0.2 control VT, p=0.07). Day 14 histological analysis revealed significantly reduced vein wall injury in statin-treated animals (thickness, 32±9.4 μm statin; vs. 56.2±14.7 μm control, p=0.02). Day 2 FDG-PET inflammation in VT correlated positively with the magnitude of day 14 VWS (jugular VT, Spearman r=0.62, p=0.02; IVC VT r=0.74, p<0.001, respectively). Conclusions: Quantitative FDG-PET/CT imaging demonstrates that early in vivo VT inflammation predicts subsequent VWS, a driver of post-thrombotic syndrome (PTS). The overall findings strengthen: (i) the link between inflammation and PTS; (ii) the translational potential of FDG-PET inflammation to predict VWS and PTS; and (iii) the concept that statins and other anti-inflammatory therapies could reduce VWS and PTS.

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Abstract 11890: S100A8/A9 is Increased in Psoriasis Serum, Relates to Vascular Diseases and Activates Human Endothelial Cells

Circulation ◽

10.1161/circ.132.suppl_3.11890 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Heather Teague ◽

Qimin Ng ◽

Monica Purmalek ◽

Balaji Natarajan ◽

Taufiq Salahuddin ◽

...

Keyword(s):

Endothelial Cells ◽

Fdg Pet ◽

Vascular Inflammation ◽

Vascular Diseases ◽

Aortic Endothelial Cells ◽

Pet Ct ◽

Calcified Plaque ◽

Fdg Pet Ct ◽

Psoriasis Severity

Introduction: Psoriasis is a chronic inflammatory disorder of the skin affecting 2-4% of the population and is associated with an increased risk of cardiovascular events, specifically myocardial infarction. Methods: In a large, ongoing prospective cohort study of psoriasis and cardiovascular diseases (NCT01778569), we studied a consecutive sample (n=100) and aimed to investigate the potential role that S100A8/A9 may have in linking psoriasis to CV disease measured by FDG PET CT and coronary CTA. Furthermore, we conducted in vitro experiments on human aortic endothelial cells (ECs) to examine whether treatement with S100A9 activates these cells. We hypothesized that S100A8/A9 would relate to psoriasis severity, relate to in vivo vascular inflammation by FDG PET CT, non-calcified burden of coronary disease by CCTA and increase endothelial cell activation. Results: We observed that the S100A8/A9 heterodimer was elevated in serum (mean psoriasis: 2019 ± 100.1; non-psoriasis: 1634 ± 160.7; p = 0.02), correlating both with psoriasis severity score (adjusted β = 0.53, p = 0.02) and overall aortic vascular inflammation measured by FDG PET CT (adjusted β = 0.48, p = 0.02) beyond the Framingham Risk Score. Additionally, we found that S100A8/A9 was associated with direct coronary atherosclerosis measured by coronary CTA demonstrating an increase in total (β = 0.16, p = 0.04) and non-calcified plaque burden (β = 0.23, p = 0.003) but not dense calcified burden. When EC's were treated with S100A9, ICAM1, E-Selectin and VCAM1 gene expression levels increased 10-fold (p = 0.001), 86-fold (P = 0.007) and 20-fold (p = 0.0002) respectively compared to the untreated human aortic endothelial cells. Conclusions: S100A8/A9 related to psoriasis severity, in vivo vascular inflammation, non-calcified plaque in the coronary arteries and EC activation. These findings suggest this protein may play a role in linking psoriasis to CVD and a role in early atherosclerotic plaque formation. Ongoing studies aim to elucidate the source of S100A8/A9 in the blood and to characterize the signaling pathway utilized by S100A8/A9 to understand whether this pathway is broadly applicable to vascular diseases associated with chronic inflammation.

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Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

Scientific Reports ◽

10.1038/s41598-020-74226-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tobias Lindner ◽

Jan Stenzel ◽

Nicole Koslowski ◽

Alexander Hohn ◽

Änne Glass ◽

...

Keyword(s):

Mouse Model ◽

Schistosoma Mansoni ◽

Fdg Pet ◽

Multimodal Imaging ◽

Organ Damage ◽

Ct Imaging ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Anatomical Mri

Abstract Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.

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18[F]FDG-PET/CT is a Useful Molecular Marker in Evaluating Tumour Aggressiveness: A Revised Understanding of an In-Vivo FDG-PET Imaging that Alludes the Alteration of Cancer Biology

Cell Biochemistry and Biophysics ◽

10.1007/s12013-012-9395-5 ◽

2012 ◽

Vol 66 (1) ◽

pp. 37-43 ◽

Cited By ~ 15

Author(s):

F. Fathinul ◽

A. J. Nordin ◽

W. F. E. Lau

Keyword(s):

Molecular Marker ◽

Pet Imaging ◽

Fdg Pet ◽

Cancer Biology ◽

Pet Ct ◽

Fdg Pet Ct

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Post-treatment alterations in 18F-dihydrotestosterone (FDHT) and FDG PET/CT in metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5073 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5073-5073 ◽

Cited By ~ 1

Author(s):

Josef J. Fox ◽

Eric C. Haupt ◽

John Humm ◽

Karen A. Autio ◽

Dana E. Rathkopf ◽

...

Keyword(s):

Prostate Cancer ◽

Fdg Pet ◽

Kinase Inhibitor ◽

Post Treatment ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Fdg Pet Ct ◽

Response Biomarkers ◽

Clinical Trial Information

5073 Background: Cabo is a multitargeted kinase inhibitor that has demonstrated complete and partial responses in mCRPC as assessed byTc-99 MDP bone scintigraphy. FDG and FDHT PET/CT demonstrate glucose metabolism and androgen receptor binding, respectively. We are exploring these tracers as response biomarkers in mCRPC treated with cabo. Methods: Patients (pts) treated with cabo were scanned with FDHT and FDG PET at baseline and after 6, 12, and 24 weeks (wks) of treatment. 5 index lesions were selected at baseline for each PET modality. The hottest slices from each were averaged (SUVmaxavg) and measured on post-treatment scans. The concordance of the post-treatment alterations of the two tracers (rise vs. decline) was examined, as were PSA alterations. Results: All 16 pts had FDG avid and 15 had FDHT avid disease. Baseline median FDHTmaxavg was 10.84 (3.52 – 18.52) and FDGmaxavg was 6.26 (2.74 – 14.7). Post-treatment alterations are described (Table). Conclusions: Most pts with mCRPC demonstrate diminution of FDHT uptake after 6 and 12 wks of treatment with cabo. These declines are matched by FDG 50-60% of the time, and correlate with PSA declines even less frequently. The etiology of the extent and degree of FDHT declines, and lack of concordance with post-treatment PSA changes, warrant further investigation, and correlation with other imaging modalities and clinical outcomes. Clinical trial information: NCT00588185. [Table: see text]

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