Gallium-68 citrate PET/CT findings in an experimental model of acute appendicitis in rabbits

Abstract Objective Acute appendicitis (AA) is the most common abdominal surgical emergency worldwide. Several infection and inflammation imaging methods have been used in a limited number of cases. Gallium-68 ( 68 Ga) has recently been investigated as an infection and inflammation imaging agent. The aim of our study was to produce 68 Ga-citrate in an automated synthesis unit and perform 68 Ga-citrate PET/CT imaging in rabbits with experimentally induced AA. Furthermore, this study aimed to investigate and correlate PET/CT findings with those of histopathological and biochemical examinations. Methods 68 Ga-citrate was synthesized using the cationic method in an automatic synthesis unit. Twelve rabbits of the New Zealand strain ( Oryctolagus cuniculus ) were divided into two groups. In the AA group (n = 6), the appendices of the rabbits were surgically ligated. In the sham group (n = 6), the abdomen was surgically opened and closed. All rabbits were imaged using 68 Ga-citrate PET/CT at 12, 24 and 36 h following the establishment of the experimental models, and at 36 h, all rabbits were appendectomised. Appendices were examined histopathologically and blood samples were drawn from all rabbits at the beginning and end of the experimental process. Interleukin-6 (IL-6) and procalcitonin (Pct) levels were measured. PET/CT results were compared statistically with histopathological and biochemical references. Results The labelling efficiency of 68 Ga-citrate was more than 98%. The sensitivity, specificity and accuracy of 68 Ga-citrate PET/CT in AA were 100%, 83.3% and 81.7%, respectively. IL-6 and Pct levels at 36 h in the AA group were significantly higher than those in the sham group and at baseline (p < 0.05). Conclusions 68 Ga-citrate was synthesized in an automatic synthesis unit for the first time, and 68 Ga-citrate uptake was shown using PET/CT in a histopathologically and biochemically confirmed experimental AA rabbit model.

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Gallium-68 PET: A Powerful Generator-based Alternative to Infection and Inflammation Imaging

Seminars in Nuclear Medicine ◽

10.1053/j.semnuclmed.2016.04.005 ◽

2016 ◽

Vol 46 (5) ◽

pp. 436-447 ◽

Cited By ~ 16

Author(s):

Mariza Vorster ◽

Alex Maes ◽

Christophe van de Wiele ◽

Mike Sathekge

Keyword(s):

Inflammation Imaging ◽

Infection And Inflammation ◽

Gallium 68

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Detection of Pulmonary Embolism with Gallium-68 Macroaggregated Albumin Perfusion PET/CT: An Experimental Study in Rabbits

10.21203/rs.3.rs-17621/v3 ◽

2020 ◽

Author(s):

Aziz Gültekin ◽

Mustafa Çağdaş Çayır ◽

Ayşe Uğur ◽

Ferda Bir ◽

Doğangün Yüksel

Keyword(s):

Ct Perfusion ◽

Rabbit Model ◽

Histopathological Analysis ◽

Model Study ◽

Ventilation Imaging ◽

Pet Ct ◽

Medicine Physician ◽

Animal Model Study ◽

Gallium 68 ◽

Sensitivity Specificity

Abstract This study was designed to evaluate the accuracy of to detect pulmonary emboli (PE) the Technegas SPECT/CT combined with 68Ga PET/CT in a rabbit model. One hour after artificial PE (n=6) and sham (n=6) models were created, Technegas SPECT/CT ventilation and 68Ga-MAA PET/CT perfusion scan (V/Q scan) were performed. All cases were performed ventilation imaging first. Technegas SPECT/CT and 68Ga-MAA PET/CT images were evaluated by a nuclear medicine physician who recorded the presence, number, and location of PE on a per-lobe basis. The sensitivity, specificity, and accuracy of Technegas SPECT/CT and 68Ga-MAA PET/CT for detecting PE were calculated using a histopathological evaluation as a reference standard.A total of 60 lung lobes were evaluated in 12 rabbits, and PE was detected in 20 lobes in V/Q scans and histopathological analysis. The overall sensitivity, specificity and accuracy were 100%, 100%, and 100%, respectively, for both the Technegas SPECT/CT and 68Ga-MAA PET/CT V/Q scans. Technegas/68Ga-MAA V/Q scans have good sensitivity, specificity and accuracy in the detection of PE in this animal model study.

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Detection of Pulmonary Embolism with Gallium-68 Macroaggregated Albumin Perfusion PET/CT: An Experimental Study in Rabbits

10.21203/rs.3.rs-17621/v2 ◽

2020 ◽

Author(s):

Aziz Gültekin ◽

Mustafa Çağdaş Çayır ◽

Ayşe Uğur ◽

Ferda Bir ◽

Doğangün Yüksel

Keyword(s):

Ct Perfusion ◽

Rabbit Model ◽

Histopathological Analysis ◽

Model Study ◽

Ventilation Imaging ◽

Pet Ct ◽

Medicine Physician ◽

Animal Model Study ◽

Gallium 68 ◽

Sensitivity Specificity

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P1215Non-invasive angiogenesis assessment with PET/CT in a rabbit model of myocardial infarction: feasibility and comparison with molecular markers

European Heart Journal ◽

10.1093/eurheartj/ehz748.0174 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C E Grandjean ◽

A Korshin ◽

M Smerup ◽

J K Jensen ◽

B Follin ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Molecular Imaging ◽

Sham Group ◽

Ex Vivo ◽

Healing Process ◽

Rabbit Model ◽

Infarct Area ◽

Pet Ct ◽

Gene Expression Alterations

Abstract Background Translational molecular imaging using Positron Emission Tomography/Computed Tomography (PET/CT) and Transesophageal Echocardiography (TEE) are powerful non-invasive tools for investigation and monitoring of cardiovascular functions. Following myocardial infarction (MI), formation of new blood vessels (angiogenesis) is of importance in the healing process and can be assessed with the PET tracer 68Ga-NODAGA-E[(cRGDyK)]2 (68Ga-RGD). Purpose The purpose of the study was to assess angiogenesis in a rabbit model of myocardial infarction using molecular imaging (PET/CT) and furthermore to validate the findings using TEE, immunohistochemistry (IHC) and quantitative PCR (qPCR). Methods Ten NZW rabbits were used (MI: n=5, SHAM: n=5). Angiogenesis was assessed with 68Ga-RGD before, 1 and 3 weeks after interventions using PET/CT (Inveon System, Siemens Health Care). TEE was used per-operatively and at termination for assessment of the MI (S8–3T probe, iE33 System, Phillips). Following the final scans, hearts were harvested for ex vivo analyses. Short axis slides were stained for collagen deposition and myocardial differentiation (H&E and Masson's trichrome), endothelial cells (CD31), and macrophage infiltration (RAM11). Gene expression alterations related to wound healing response (inflammation, granulation, and tissue remodeling) were measured using qPCR arrays (84 genes analyzed). Results One week after the interventions, 68Ga-RGD uptake, as assessed with PET was increased in the infarct area when compared to the remote zone of the same rabbit as well as compared to the SHAM group. Three weeks after intervention, there was no difference in 68Ga-RGD uptake between groups. High quality TEE images were obtained in all rabbits. Ex vivo analyses at 3 weeks after intervention revealed moderate vessel formation (CD31) in the infarct zone, none in the border zone, whereas surrounding viable myocardium had visible CD31 positive vessels comparable to the SHAM group. Macrophage infiltration (RAM11) and collagenous scaring (Masson's trichrome) was pronounced in the infarcted area. Gene expression alterations in the infarct area (30 of 84 genes upregulated) were dominated by increased expression of collagens (COL1A2, COL5A1, COL5A4), inflammatory chemokines and cytokines (CCL2, IL1A, IL1B, IL6, IL10) and ECM remodeling enzymes (uPAR, TPA, TIMP1, SERPINE1, MMP9) in the MI group compared to the SHAM group, whereas integrins involved in the angiogenesis response (ITGA4, ITGAV) were only moderately changed in the infarction at termination, confirming the in vivo PET findings. Study outline Conclusions In this rabbit MI model, we demonstrate the feasibility of monitoring angiogenesis in the healing process non-invasively with PET. The imaging results were confirmed by IHC and gene expression analysis. Moreover, TEE using a dedicated pediatric probe is feasible in the rabbit model, making this a robust and translational medium-sized animal model of myocardial infarction.

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Past and Future of Ga-citrate for Infection and Inflammation Imaging

Current Pharmaceutical Design ◽

10.2174/1381612824666171129200611 ◽

2018 ◽

Vol 24 (7) ◽

pp. 787-794 ◽

Cited By ~ 3

Author(s):

Mariza Vorster ◽

John Buscombe ◽

Ziauddin Saad ◽

Mike Sathekge

Keyword(s):

Wide Spectrum ◽

Lessons Learned ◽

Added Value ◽

Current Status ◽

Clinical Settings ◽

Anatomical Imaging ◽

Pet Ct ◽

Inflammation Imaging ◽

Infection And Inflammation ◽

Increasing Demand

Both 67Ga and 68Ga-citrates are used to detect a wide spectrum of pathology consisting of various inflammatory, infectious and malignant conditions. Considering the now widespread availability and constantly increasing demand for PET/CT studies,68Ga-citrate is gaining ground in clinical settings and the added value of combined metabolic and anatomical imaging achieved by combining PET with Computed Tomography (CT) to PET/CT makes 68Ga-citrate particularly promising. Despite the tracer's non-specificity, it has demonstrated potential especially in the evaluation of various infectious and inflammatory skeletal- and lung conditions. In this review, we will focus on the indications and lessons learned from 67Ga, and present the current status for the use of 68Ga-citrate PET/CT in selected inflammation and infectious diseases based on the limited literature available.

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Detection of Pulmonary Embolism with Gallium-68 Macroaggregated Albumin Perfusion PET/CT: An Experimental Study in Rabbits

Contrast Media & Molecular Imaging ◽

10.1155/2020/5607951 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Aziz Gültekin ◽

Mustafa Çağdaş Çayır ◽

Ayşe Uğur ◽

Ferda Bir ◽

Doğangün Yüksel

Keyword(s):

Pulmonary Embolism ◽

Ct Perfusion ◽

Rabbit Model ◽

Histopathological Analysis ◽

Model Study ◽

Pet Ct ◽

Medicine Physician ◽

Animal Model Study ◽

Gallium 68 ◽

Sensitivity Specificity

This study was designed to evaluate the accuracy of detecting pulmonary embolism (PE) using the Technegas SPECT/CT combined with 68Ga PET/CT in a rabbit model. One hour after artificial PE (n = 6) and sham (n = 6) models were created, Technegas SPECT/CT ventilation and 68Ga-MAA PET/CT perfusion scan (V/Q scan) were performed. Ventilation imaging was performed first on all cases. Technegas SPECT/CT and 68Ga-MAA PET/CT images were evaluated by a nuclear medicine physician who recorded the presence, number, and location of PE on a per-lobe basis. The sensitivity, specificity, and accuracy of Technegas SPECT/CT and 68Ga-MAA PET/CT for detecting PE were calculated using a histopathological evaluation as a reference standard. A total of 60 lung lobes were evaluated in 12 rabbits, and PE was detected in 20 lobes in V/Q scans and histopathological analysis. The overall sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively, for both the Technegas SPECT/CT and 68Ga-MAA PET/CT V/Q scans. Technegas/68Ga-MAA V/Q scans have good sensitivity, specificity, and accuracy in the detection of PE in this animal model study.

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Comparison of Fluorine(18)-fluorodeoxyglucose and Gallium(68)-citrate PET/CT in patients with tuberculosis

Nuklearmedizin ◽

10.1055/a-1000-6951 ◽

2019 ◽

Vol 58 (05) ◽

pp. 371-378

Author(s):

Alfred O. Ankrah ◽

Ismaheel O. Lawal ◽

Tebatso M.G. Boshomane ◽

Hans C. Klein ◽

Thomas Ebenhan ◽

...

Keyword(s):

Tracer Uptake ◽

Pet Ct ◽

The Mean ◽

18F Fdg ◽

Definition Of ◽

Gallium 68 ◽

Attending Physician ◽

Pet Scans ◽

The Brain

Abstract 18F-FDG and 68Ga-citrate PET/CT have both been shown to be useful in the management of tuberculosis (TB). We compared the abnormal PET findings of 18F-FDG- and 68Ga-citrate-PET/CT in patients with TB. Methods Patients with TB on anti-TB therapy were included. Patients had a set of PET scans consisting of both 18F-FDG and 68Ga-citrate. Abnormal lesions were identified, and the two sets of scans were compared. The scan findings were correlated to the clinical data as provided by the attending physician. Results 46 PET/CT scans were performed in 18 patients, 11 (61 %) were female, and the mean age was 35.7 ± 13.5 years. Five patients also had both studies for follow-up reasons during the use of anti-TB therapy. Thirteen patients were co-infected with HIV. 18F-FDG detected more lesions than 68Ga-citrate (261 vs. 166, p < 0.0001). 68Ga-citrate showed a better definition of intracerebral lesions due to the absence of tracer uptake in the brain. The mean SUVmax was higher for 18F-FDG compared to 68Ga-citrate (5.73 vs. 3.01, p < 0.0001). We found a significant correlation between the SUVmax of lesions that were determined by both tracers (r = 0.4968, p < 0.0001). Conclusion Preliminary data shows 18F-FDG-PET detects more abnormal lesions in TB compared to 68Ga-citrate. However, 68Ga-citrate has better lesion definition in the brain and is therefore especially useful when intracranial TB is suspected.

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