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Europe PubMed Central
Article . 2020
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Journal of Nuclear Medicine
Article . 2020
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Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI

Hicham Skali; Venkatesh L. Murthy; Mouaz H. Al-Mallah; Tim M. Bateman; Rob Beanlands; Nathan Better; Dennis A. Calnon; +8 Authors

Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI

Abstract

1022 Purpose: The programmed death-ligand 1 (PD-L1) immunohistochemistry correlates moderately with the response to PD-L1 immunomodulatory therapy. Here we present the initial results from the studies to assess the feasibility of non-invasive PD-L1 imaging with 68Ga-WL12 (a 12-mer anti-PD-L1 peptide) radiotracer from animal experiments to the first-in-human study. Methods: PD-L1 binding peptide, NOTA-WL12, was synthesized by custom services with >95% chemical purity. , we generated 68Ga-WL12 with high specific radioactivity and radiochemical purity. We select human non-small cell lung cancer cells ( HCC827) , which with moderate expression of PD-L1. To demonstrate PD-L1-specific binding of 68Ga-WL12, both binding affinity test and cell uptakes were carried out with excess WL12. Normal Mice were used for PET/CT imaging and biodistribution study. Finally, we recruited a patient ( 80 years old female ;ethical approval No.2019KT) with non-small cell lung cancer who was positive for PD-L1(>80%) and performed PET/CT imaging with 68Ga-WL12 before and after immunomodulatory therapy. Results: To demonstrate PD-L1 specificity and cell uptake, we generated 68Ga-WL12 with radiochemical purity >99% after purification, specific activity 27.8-111.2 GBq/umol. High 68Ga-WL12 uptake was observed in PD-L1-positive HCC827 cells. TO confirming radiotracer specificity, we observed a significant reduction in bound 68Ga-WL12 in the presence of the excess unmodified peptide, indicating that 68Ga-WL12 binding to PD-L1 is specific. We performed PET imaging of the tumor model with 68Ga-WL12. The uptake value was consistent with tracer biodistribution. Finally, in this first-in-human assessment of 68Ga-WL12, we show that the imaging signal corresponds to PD-L1 expression at sites of the primary tumor and metastatic focus. The SUVpeak of different tumor lesions ranged from 2.0 to 6.0. The SUV value of PD-L1 positive tumors decreased significantly after immunomodulatory therapy. Conclusions: In this study, we demonstrated that 68Ga-WL12 exhibited a high affinity to PD-L1 in the Cell uptake experiment in vitro. 68Ga-WL12 demonstrated PD-L1 specific uptake first-in-human study. Therefore, 68Ga-WL12 PET/CT imaging may be a useful tool to assess PD-L1 expression in lesions. Future clinical studies are needed to confirm our findings in a larger patient population, to comprehensively assess different 68Ga-WL12 uptake features in combination with other clinical data to optimize therapy response prediction, and to evaluate whether 68Ga-WL12 PET could also be used as a response predictor for treatment with other monoclonal antibodies targeting the PD-1/PD-L1 axis.

Subjects by Vocabulary

Microsoft Academic Graph classification: Cell medicine.anatomical_structure medicine Cancer research Specific activity Imaging Signal In vitro Primary tumor medicine.disease Immunohistochemistry business.industry business Biodistribution Monoclonal antibody medicine.drug_class

Keywords

Radiology, Nuclear Medicine and imaging, Information Statement, Betacoronavirus, COVID-19, Cardiology, Coronavirus Infections, Humans, Nuclear Medicine, Pandemics, Pneumonia, Viral, Practice Guidelines as Topic, SARS-CoV-2, nuclear cardiology, Cardiology and Cardiovascular Medicine, Radiology Nuclear Medicine and imaging

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    53
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Substantial
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    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
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