scholarly journals Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis

2021 ◽  
Vol 8 ◽  
Author(s):  
Arghavan Jahandideh ◽  
Mia Ståhle ◽  
Jenni Virta ◽  
Xiang-Guo Li ◽  
Heidi Liljenbäck ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Cell Surface Receptor ◽  
Myocardial Inflammation ◽  
Autoimmune Myocarditis ◽  
Inflammatory Lesions ◽  
Pet Tracer ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

The 68Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([68Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor αvβ3 integrin that is upregulated during angiogenesis and inflammation. We studied whether αvβ3 targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [68Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [68Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUVmean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [68Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing αvβ3 integrin-positive capillary-like structures. A non-specific [68Ga]Ga-DOTA-(RGE)2 tracer showed 76% lower uptake than [68Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that αvβ3 integrin-targeting [68Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.

Dose Formulation, Biodistribution and PET Imaging Studies of a First-In-Class Fluorine-18 Organophosphorus Cholinesterase Inhibitor Tracer in Rat

2020 ◽  
Vol 14 ◽  
Author(s):  
Kiel D. Neumann ◽  
Joseph E. Blecha ◽  
Chih-Kai Chao ◽  
Tony Huynh ◽  
Kurt R. Zinn ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Male Rats ◽  
Imaging Data ◽  
Live Tissue ◽  
Dose Formulation ◽  
Pet Tracer ◽  
Ex Vivo Biodistribution

Background:: To investigate dynamic live tissue organophosphorus nerve agent uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported the first-in-class fluorine-18 (18F) radiolabeled positron emission tomography (PET) imaging tracer known as [18F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer has been initially studied in live rats with PET imaging. Objective.: We sought to evaluate the PET tracer in vivo using a new dose formulation of saline, ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo tracer performance to previous data collected using a CH3CN:PBS formulation. Methods:: A high molar activity [18F] tracer radiosynthesis was used. Doses were formulated as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6 h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data were compared. Results and Discussion:: An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable doses for 6 h (>99%). Arterial blood included tracer and a single metabolite. The ex vivo biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed tissue levels: heart and lung, highest; liver, moderate; and brain, lowest. Conclusions:: Imaging and biodistribution data were highly correlated with expected radioactivity tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as compared to the established CH3CN:PBS formulation. Overall, we find that the i.v. dose formulation changed the in vivo profile of an organophosphorus PET tracer is considered an important finding for future organophosporus PET tracer studies.

scholarly journals Berberine Delays Onset of Collagen-Induced Arthritis through T Cell Suppression

2021 ◽  
Vol 22 (7) ◽  
pp. 3522
Author(s):  
Alexandra A. Vita ◽  
Hend Aljobaily ◽  
David O. Lyons ◽  
Nicholas A. Pullen
Keyword(s):  
T Cell ◽  
Type Ii Collagen ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Preclinical Phase ◽  
T Cell Suppression ◽  
Cell Suppression ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

There is evidence that berberine (BBR), a clinically relevant plant compound, ameliorates clinically apparent collagen-induced arthritis (CIA) in vivo. However, to date, there are no studies involving the use of BBR which explore its prophylactic potential in this model of rheumatoid arthritis (RA). The aim of this study was to determine if prophylactic BBR use during the preclinical phase of collagen-induced arthritis would delay arthritic symptom onset, and to characterize the cellular mechanism underlying such an effect. DBA/1J mice were injected with an emulsion of bovine type II collagen (CII) and complete Freund’s adjuvant (day 0) and a booster injection of CII in incomplete Freund’s adjuvant (day 18) to induce arthritis. Mice were then given i.p. injections of 1 mg/kg/day of BBR or PBS (vehicle with 0.01% DMSO) from days 0 to 28, were left untreated (CIA control), or were in a non-arthritic control group (n = 15 per group). Incidence of arthritis in BBR-treated mice was 50%, compared to 90% in both the CIA and PBS controls. Populations of B and T cells from the spleens and draining lymph nodes of mice were examined on day 14 (n = 5 per group) and day 28 (n = 10 per group). BBR-treated mice had significantly reduced populations of CD4+Th and CD4+CXCR5+ Tfh cells, and an increased proportion of Foxp3+ Treg at days 14 and 28, as well as reduced expression of co-stimulatory molecules CD28 and CD154 at both endpoints. The effect seen on T cell populations and co-stimulatory molecule expression in BBR-treated mice was not mirrored in CD19+ B cells. Additionally, BBR-treated mice experienced reduced anti-CII IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement for RA, and that its effect may be mediated specifically through T cell suppression. However, the cellular effector involved raises concern for BBR prophylactic use in the context of vaccine efficacy and other primary adaptive immune responses.

scholarly journals Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Durga M. S. H. Chandrupatla ◽  
Gerrit Jansen ◽  
Elise Mantel ◽  
Philip S. Low ◽  
Takami Matsuyama ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Folate Receptor ◽  
Tracer Uptake ◽  
Response Monitoring ◽  
Distribution Analysis ◽  
Pet Tracer ◽  
Systemic Inflammatory Disease ◽  
Before And After

Background. In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptorβ(FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment.Methods. [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβexpression.Results. [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p<0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p<0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold,p<0.005) and spleen (3-fold,p<0.01) of MTX- versus saline-treated rats.Conclusions. MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.

Designed multifunctional polymeric nanomedicines: long-term biodistribution and tumour accumulation of aptamer-targeted nanomaterials

2018 ◽  
Vol 54 (82) ◽  
pp. 11538-11541 ◽  
Author(s):  
N. L. Fletcher ◽  
Z. H. Houston ◽  
J. D. Simpson ◽  
R. N. Veedu ◽  
K. J. Thurecht
Keyword(s):  
Polyethylene Glycol ◽  
Pet Imaging ◽  
Hyperbranched Polymer ◽  
Ex Vivo

We report a novel multifunctional hyperbranched polymer based on polyethylene glycol (PEG) as a nanomedicine platform that facilitates longitudinal and quantitative 89Zr-PET imaging, enhancing knowledge of nanomaterial biodistribution and pharmacokinetics/pharmacodynamics both in vivo and ex vivo.

Abstract 2876: Early Retention and Subsequent Engraftment of Transplanted Progenitor Cells is Improved by Delivery within Collagen Matrix

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yan Zhang ◽  
Marc Lamoureux ◽  
Stephanie Thorn ◽  
Vincent Chan ◽  
Joel Price ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Progenitor Cells ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Collagen Matrix ◽  
Cell Labeling ◽  
Type I ◽  
The Matrix ◽  
Early Retention

Background: To investigate the mechanisms involved in the potentiation of cell therapy by delivery matrices, we evaluated the retention and engraftment of transplanted human circulating progenitor cells (CPCs) injected in a collagen matrix by using in vivo positron emission tomography (PET) imaging, ex vivo biodistribution, and immunohistochemistry. Methods: CPCs were labeled with 18 F-FDG and injected with or without a collagen type I-based matrix in the ischemic hindlimb muscle (IM) of rats (2x10 6 cells; n=15/group). Localization of cells was acquired by PET imaging (15 min) at 150 min post-injection. In addition, radionuclide biodistribution, immunofluorescence, and immunohistochemical examination of transplanted CPCs were performed at up to 14 days. Results: Cell labeling efficiency was CPC-concentration dependent (r=0.61, p <0.001), but not 18 F-FDG-dose dependent. Labeled CPCs exhibited excellent short-term stability and viability. Persistence of 18 F-FDG radioactivity in cells was markedly greater than non-specific retention in the matrix. Wholebody (WB) PET images revealed better CPC retention in the IM and less non-specific leakage to other tissues when CPCs were delivered within the matrix (IM/WB retention ratio of 43.9±8.2%), compared to cells injected alone (22.3±10.4%; p =0.040) and to 18 F-FDG injected with or without the matrix (9.7±5.5% and 11.0±5.5%, respectively; p <0.005). Radioactivity biodistribution confirmed that accumulation was increased (by 92.5%; p =0.024) in the IM and reduced (by 1.1 to 23.8%; p <0.05) in non-specific tissues when cells were injected within the matrix, compared to cells injected alone. Anti-human mitochondria staining showed increased cell retention in the IM with use of matrices (3.0±2.1%) versus cells only (1.9±0.8%; p =0.048). At 14 days the number of CD31 + transplanted human cells was greater (1.6±0.1%) when injected within the matrix than injected alone (0.7±0.1%; p =0.004). Conclusions: Collagen-based delivery matrices improve the early retention of transplanted CPCs, which in turn favors subsequent cell engraftment in the ischemic tissue. This mechanism conferred by the matrix has potential implications for the optimization of cell therapy at the early stages after cell delivery.

scholarly journals Terminalia tomentosa Bark Ameliorates Inflammation and Arthritis in Carrageenan Induced Inflammatory Model and Freund’s Adjuvant-Induced Arthritis Model in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Srinivasa Reddy Jitta ◽  
Prasanthi Daram ◽  
Karthik Gourishetti ◽  
C. S. Misra ◽  
Picheswara Rao Polu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Complete Freund’S Adjuvant ◽  
Inflammatory Activity ◽  
Aqueous Extracts ◽  
Adjuvant Induced Arthritis ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant ◽  
Anti Inflammatory

Terminalia tomentosa bark belongs to the family Combretaceae. The plant bark is astringent and useful in the treatment of ulcers, vata, fractures, hemorrhages, bronchitis, and diarrhea. Phytochemical investigation of T. tomentosa bark confirms the presence of flavonoids, polyphenols, and tannins. The plant has not been investigated for its anti-inflammatory and antiarthritic activity. The present study was undertaken to explore its possible anti-inflammatory and antiarthritic activity. Anti-inflammatory activity of alcoholic and aqueous extracts of the bark was assessed by in vivo methods. In vivo antiarthritic potential of the extracts was evaluated by Complete Freund’s Adjuvant (CFA) induced arthritis in Wistar rats. Our findings showed that the alcoholic and aqueous extracts exhibited anti-inflammatory activity at 500 mg/kg oral dose in carrageenan-induced hind paw edema and carrageenan-induced air pouch inflammation models. We also found alcoholic as well as aqueous extracts of the bark restored the altered blood and serum parameters caused by the Complete Freund’s Adjuvant-induced arthritis in Wistar rats. This study shows that the T. tomentosa bark extracts possess anti-inflammatory activity and have pronounced effects on adjuvant arthritis also. Future studies are necessary to provide deeper insight into the exact mechanism of the action of anti-inflammatory and antiarthritic activity of T. tomentosa.

scholarly journals Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumour models using a site-specifically labelled PD-L1 antibody

2019 ◽  
Vol 47 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Camilla Christensen ◽  
Lotte K. Kristensen ◽  
Maria Z. Alfsen ◽  
Carsten H. Nielsen ◽  
Andreas Kjaer
Keyword(s):  
Pet Imaging ◽  
Predictive Value ◽  
Ex Vivo ◽  
Response To Therapy ◽  
Whole Body ◽  
Therapeutic Monitoring ◽  
Non Invasive ◽  
Tumour Bearing ◽  
Quantitative Pet

Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value. Methods Anti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade. Results 89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252). Conclusion PET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.

scholarly journals Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [11C]ABP688 PET imaging and ex vivo immunoblotting

2017 ◽  
Vol 113 ◽  
pp. 293-300 ◽  
Author(s):  
Xiaotian T. Fang ◽  
Jonas Eriksson ◽  
Gunnar Antoni ◽  
Ulrika Yngve ◽  
Linda Cato ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Pet Imaging ◽  
Ex Vivo

scholarly journals Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Radiochemical Yield ◽  
Control Group ◽  
Complexing Agent ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Pet Ct

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

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