scholarly journals Comparison of: (2S,4R)-4-[18F]Fluoroglutamine, [11C]Methionine, and 2-Deoxy-2-[18F]Fluoro-D-Glucose and Two Small-Animal PET/CT Systems Imaging Rat Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Maxwell W. G. Miner ◽  
Heidi Liljenbäck ◽  
Jenni Virta ◽  
Semi Helin ◽  
Olli Eskola ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Kinetic Modelling ◽  
Small Animal ◽  
Small Animal Pet ◽  
Dynamic Pet ◽  
Pharmacokinetic Models ◽  
Total Blood ◽  
Pet Ct ◽  
Significant Difference

PurposeThe three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.ProceduresUp to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models.ResultsAverage BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25).ConclusionsIn orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.

scholarly journals A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5819
Author(s):  
Lisa Russelli ◽  
Francesco De Rose ◽  
Loredana Leone ◽  
Sybille Reder ◽  
Markus Schwaiger ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Small Animal ◽  
Biologically Active ◽  
Small Animal Pet ◽  
Organ Distribution ◽  
Complexing Agent ◽  
Distribution Studies

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.

scholarly journals 18F-labeled tracers targeting fibroblast activation protein

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Thomas Lindner ◽  
Annette Altmann ◽  
Frederik Giesel ◽  
Clemens Kratochwil ◽  
Christian Kleist ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Pet Imaging ◽  
Small Animal ◽  
Fibroblast Activation Protein ◽  
Small Cell ◽  
Small Animal Pet ◽  
Small Cell Lung ◽  
Pet Ct

Abstract Background Cancer-associated fibroblasts are found in the stroma of epithelial tumors. They are characterized by overexpression of the fibroblast activation protein (FAP), a serine protease which was already proven as attractive target for chelator-based theranostics. Unfortunately, the value of gallium-68 labeled tracers is limited by their batch size and the short nuclide half-life. To overcome this drawback, radiolabeling with aluminum fluoride complexes and 6-fluoronicotinamide derivatives of the longer-lived nuclide fluorine-18 was established. The novel compounds were tested for their FAP-specific binding affinity. Uptake and binding competition were studied in vitro using FAP expressing HT-1080 cells. HEK cells transfected with the closely related dipeptidyl peptidase-4 (HEK-CD26) were used as negative control. Small animal positron emission tomography imaging and biodistribution experiments were performed in HT-1080-FAP xenografted nude mice. [18F]AlF-FAPI-74 was selected for PET/CT imaging in a non-small cell lung cancer (NSCLC) patient. Results In vitro, 18F-labeled FAPI-derivatives demonstrated high affinity (EC50 = < 1 nm to 4.2 nm) and binding of up to 80% to the FAP-expressing HT1080 cells while no binding to HEK-CD26 cells was observed. While small animal PET imaging revealed unfavorable biliary excretion of most of the 18F-labeled compounds, the NOTA bearing compounds [18F]AlF-FAPI-74 and -75 achieved good tumor-to-background ratios, as a result of their preferred renal excretion. These two compounds showed the highest tumor accumulation in PET imaging. The organ distribution values of [18F]AlF-FAPI-74 were in accordance with the small animal PET imaging results. Due to its less complex synthesis, fast clearance and low background values, [18F]AlF-FAPI-74 was chosen for clinical imaging. PET/CT of a patient with metastasized non-small cell lung cancer (NSCLC), enabled visualization of the primary tumor and its metastases at the hepatic portal and in several bones. This was accompanied by a rapid clearance from the blood pool and low background in healthy organs. Conclusion [18F]AlF-labeled FAPI derivatives represent powerful tracers for PET. Owing to an excellent performance in PET imaging, FAPI-74 can be regarded as a promising precursor for [18F]AlF-based FAP-imaging.

Evaluation of the Small-animal Nano Scan PET/CT System using 89Zr

2020 ◽  
Vol 16 ◽  
Author(s):  
Khaled Alzimami ◽  
Sitah Alanazi ◽  
Magdi Gannam ◽  
Ahmad Alanazi ◽  
Ibrahim Aljamaz ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Half Life ◽  
Small Animal ◽  
Small Animal Pet ◽  
Reconstruction Method ◽  
Ct Scanner ◽  
Animal Pet ◽  
Positron Range ◽  
Pet Ct ◽  
Significant Difference

Introduction: The purpose of the present work was to evaluate the imaging characteristics of 89Zr-PET in comparison with those obtained using fluorine-18 Fluorodeoxyglucose (18F-FDG) PET (a gold standard tracer in PET imaging) using a small-animal NanoScan PET/CT scanner. Methods: The system’s spatial resolution, sensitivity, uniformity, and image quality were measured on a Nano Scan small-animal PET/CT scanner according to the NEMA NU4-2008 protocols. For reconstruction images, we used 2D and 3D reconstruction algorithms. The reconstruction methods included filter back projection (FBP), the ordered subsets expectation maximization (OSEM) algorithm, and the 3D Tera-Tomo algorithm, which are developed for the NanoScan small-animal PET/CT scanner. Results: The results obtained showed a significant difference in the spatial resolution for 89Zr as compared to 22Na and 18F when using a 2D reconstruction algorithm. Where the spatial resolution values were much enhanced by using the 3D Tera-Tomo reconstruction for each isotope, the Full width at half maximum (FWHM) values were less than 1 for all isotopes at the center of the field of view (FOV). This difference in spatial resolution is dependent on the positron range, energy and the reconstruction method. Conclusion: The long half-life of 89Zr makes it an ideal positron emitter for performing immuno-PET, which is matched with the biological half-life of intact mAbs. 89Zr can also give several advantages over other long half-life positron emitters in relation to the overall imaging performance because of its relatively short positron range and simpler decay scheme. The values of 89Zr sensitivity that were obtained in the present study were less than those of previous studies.

Evaluation of A Novel GLP-1R Ligand for PET Imaging of Prostate Cancer

2019 ◽  
Vol 19 (4) ◽  
pp. 509-514 ◽  
Author(s):  
Yuanyuan Yue ◽  
Yuping Xu ◽  
Lirong Huang ◽  
Donghui Pan ◽  
Zhicheng Bai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Small Animal ◽  
Small Animal Pet ◽  
Great Promise ◽  
Western Blots ◽  
Biodistribution Studies

Background:Glucagon-like peptide 1 receptor (GLP-1R) is an important biomarker for diagnosis and therapy of the endocrine cancers due to overexpression. Recently, in human prostate cancer cell lines the receptor was also observed, therefore it may be a potential target for the disease. 18F-Al-NOTA-MAL-Cys39- exendin-4 holds great promise for GLP-1R. Therefore, the feasibility of the 18F-labeled exendin-4 analog for prostate cancer imaging was investigated.Methods:New probe 18F-Al-NOTA-MAL-Cys39-exendin-4 was made through one-step fluorination. Prostate cancer PC3 cell xenograft model mice were established to primarily evaluate the imaging properties of the tracer via small animal PET studies in vivo. Pathological studies and Western Blots were also performed.Results:PC-3 prostate xenografts were clearly imaged under baseline conditions. At 30 and 60 min postinjection, the tumor uptakes were 2.90±0.41%ID/g and 2.26±0.32 %ID/g respectively. The presence of cys39-exendin-4 significantly reduced the tumor uptake to 0.82±0.10 %ID/g at 60 min p.i. Findings of ex vivo biodistribution studies were similar to those of in vivo PET imaging. The tumors to blood and muscles were significantly improved with the increase of time due to rapid clearance of the tracer from normal organs. Low levels of radioactivity were also detected in the GLP-1R positive tumor and normal organs after coinjection with excessive unlabeled peptides. Immunohistochemistry and Western Blots results confirmed that GLP-1R was widely expressed in PC-3 prostate cancers.Conclusion:18F-Al labeled exendin-4 analog might be a promising tracer for in vivo detecting GLP-1R positive prostate cancer with the advantage of facile synthesis and favorable pharmacokinetics. It may be useful in differential diagnosis, molecularly targeted therapy and prognosis of the cancers.

scholarly journals Performance evaluation of an adjustable gantry PET (AGPET) for small animal PET imaging

2021 ◽  
Author(s):  
Hankyeol Song ◽  
In Soo Kang ◽  
Kyu Bom Kim ◽  
Chanwoo Park ◽  
Min Kyu Baek ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Pet Imaging ◽  
Small Animal ◽  
Small Animal Pet ◽  
Animal Pet

Development of a small animal PET imaging device with resolution approaching 1 mm

1999 ◽  
Vol 46 (3) ◽  
pp. 631-635 ◽  
Author(s):  
J.A. Correia ◽  
C.A. Burnham ◽  
D. Kaufman ◽  
A.J. Fischman
Keyword(s):  
Pet Imaging ◽  
Small Animal ◽  
Small Animal Pet ◽  
Imaging Device ◽  
Animal Pet

scholarly journals The distribution of D2/D3 receptor binding in the adolescent rhesus monkey using small animal PET imaging

NeuroImage ◽  
2009 ◽  
Vol 44 (4) ◽  
pp. 1334-1344 ◽  
Author(s):  
B CHRISTIAN ◽  
N VANDEHEY ◽  
A FOX ◽  
D MURALI ◽  
T OAKES ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Receptor Binding ◽  
Pet Imaging ◽  
Small Animal ◽  
Small Animal Pet ◽  
D3 Receptor ◽  
Animal Pet

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

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