scholarly journals Cerenkov Luminescence Imaging in the Development and Production of Radiopharmaceuticals

2021 ◽  
Vol 9 ◽  
Author(s):  
R. Michael van Dam ◽  
Arion F. Chatziioannou

Over the past several years there has been an explosion of interest in exploiting Cerenkov radiation to enable in vivo and intraoperative optical imaging of subjects injected with trace amounts of radiopharmaceuticals. At the same time, Cerenkov luminescence imaging (CLI) also has been serving as a critical tool in radiochemistry, especially for the development of novel microfluidic devices for producing radiopharmaceuticals. By enabling microfluidic processes to be monitored non-destructively in situ, CLI has made it possible to literally watch the activity distribution as the synthesis occurs, and to quantitatively measure activity propagation and losses at each step of synthesis, paving the way for significant strides forward in performance and robustness of those devices. In some cases, CLI has enabled detection and resolution of unexpected problems not observable via standard optical methods. CLI is also being used in analytical radiochemistry to increase the reliability of radio-thin layer chromatography (radio-TLC) assays. Rapid and high-resolution Cerenkov imaging of radio-TLC plates enables detection of issues in the spotting or separation process, improves chromatographic resolution (and/or allows reduced separation distance and time), and enables increased throughput by allowing multiple samples to be spotted side-by-side on a single TLC plate for parallel separation and readout. In combination with new multi-reaction microfluidic chips, this is creating a new possibility for high-throughput optimization in radiochemistry. In this mini review, we provide an overview of the role that CLI has played to date in the radiochemistry side of radiopharmaceuticals.

2020 ◽  
Author(s):  
Sheng Zhao ◽  
Wen-Bin Pan ◽  
Hui-Jie Jiang ◽  
Rong-Jun Zhang ◽  
Hao Jiang ◽  
...  

Abstract Background : Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131 I-labeled anti-PD-L1 monoclonal antibody tracer, 131 I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131 I( 131 I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131 I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131 I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131 I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10 -9 M. The competitive inhibition assay further confirmed the specific binding ability of 131 I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131 I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% ID/g at 120 h.Conclusions: There is a great potential for 131 I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Xu Cao ◽  
Yang Li ◽  
Yonghua Zhan ◽  
Xueli Chen ◽  
Fei Kang ◽  
...  

Cerenkov luminescence imaging (CLI) can provide information of medical radionuclides used in nuclear imaging based on Cerenkov radiation, which makes it possible for optical means to image clinical radionuclide labeled probes. However, the exceptionally weak Cerenkov luminescence (CL) from Cerenkov radiation is susceptible to lots of impulse noises introduced by high energy gamma rays generating from the decays of radionuclides. In this work, a temporal median filter is proposed to remove this kind of impulse noises. Unlike traditional CLI collecting a single CL image with long exposure time and smoothing it using median filter, the proposed method captures a temporal sequence of CL images with shorter exposure time and employs a temporal median filter to smooth a temporal sequence of pixels. Results of in vivo experiments demonstrated that the proposed temporal median method can effectively remove random pulse noises induced by gamma radiation and achieve a robust CLI image.


2016 ◽  
Vol 52 (86) ◽  
pp. 12745-12748 ◽  
Author(s):  
Hualong Fu ◽  
Cheng Peng ◽  
Zhigang Liang ◽  
Jiapei Dai ◽  
Boli Liu ◽  
...  

Three fluorinated (19F or 18F) small molecules were evaluated as fluorescent or radiolabeled probes for Aβ deposits in the brain.


2014 ◽  
Vol 74 (20) ◽  
pp. 5846-5854 ◽  
Author(s):  
Ethan R. Balkin ◽  
Aimee Kenoyer ◽  
Johnnie J. Orozco ◽  
Alexandra Hernandez ◽  
Mazyar Shadman ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sheng Zhao ◽  
Wenbin Pan ◽  
Huijie Jiang ◽  
Rongjun Zhang ◽  
Hao Jiang ◽  
...  

2018 ◽  
Vol 17 ◽  
pp. 153601211878863 ◽  
Author(s):  
Frezghi Habte ◽  
Arutselvan Natarajan ◽  
David S. Paik ◽  
Sanjiv Sam Gambhir

Cerenkov luminescence imaging (CLI) is commonly performed using two-dimensional (2-D) conventional optical imaging systems for its cost-effective solution. However, quantification of CLI comparable to conventional three-dimensional positron emission tomography (PET) is challenging using these systems due to both the high attenuation of Cerenkov radiation (CR) on mouse tissue and nonexisting depth resolution of CLI using 2-D imaging systems (2-D CLI). In this study, we developed a model that estimates effective tissue attenuation coefficient and corrects the tissue attenuation of CLI signal intensity independent of tissue depth and size. To evaluate this model, we used several thin slices of ham as a phantom and placed a radionuclide (89Zr and 64Cu) inside the phantom at different tissue depths and sizes (2, 7, and 12 mm). We performed 2-D CLI and MicroPET/CT (Combined small animal PET and Computed Tomography (CT)) imaging of the phantom and in vivo mouse model after administration of 89Zr tracer. Estimates of the effective tissue attenuation coefficient (μeff) for 89Zr and 64Cu were ∼2.4 and ∼2.6 cm−1, respectively. The computed unit conversion factor to %ID/g from 2-D CLI signal was 2.74 × 10−3 μCi/radiance estimated from phantom study. After applying tissue attenuation correction and unit conversion to the in vivo animal study, an average quantification difference of 10% for spleen and 35% for liver was obtained compared to PET measurements. The proposed model provides comparable quantification accuracy to standard PET system independent of deep tissue CLI signal attenuation.


2020 ◽  
Author(s):  
Sheng Zhao ◽  
Wen-Bin Pan ◽  
Hui-Jie Jiang ◽  
Rong-Jun Zhang ◽  
Hao Jiang ◽  
...  

Abstract Background: Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131I-labeled anti-PD-L1 monoclonal antibody tracer, 131I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10-9M. The competitive inhibition assay further confirmed the specific binding ability of 131I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738%IA/g at 48 h.Conclusions: There is a great potential for 131I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.


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