Development of [F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide

Autor: Wojciech G. Lesniak PhD, Ronnie C. Mease PhD, Samit Chatterjee PhD, Dhiraj Kumar PhD, Ala Lisok MA, Bryan Wharram MS, Venkateswara Rao Kalagadda PhD, Leisha A. Emens MD, PhD, Martin G. Pomper MD, PhD, Sridhar Nimmagadda PhD
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Imaging, Vol 18 (2019)
Druh dokumentu: article
ISSN: 1536-0121
15360121
DOI: 10.1177/1536012119852189
Popis: Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [ 18 F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, 19 FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC 50 ], 26-32 nM). The radiotracer, [ 18 F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[ 18 F]fluoronicotinate ([ 18 F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [ 18 F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [ 18 F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [ 18 F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.
Databáze: Directory of Open Access Journals
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