Dataset Information

Development of [¹⁸F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

ABSTRACT: 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 [¹⁸F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, ¹⁹FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC₅₀], 26-32 nM). The radiotracer, [¹⁸F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[¹⁸F]fluoronicotinate ([¹⁸F]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 [¹⁸F]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 [¹⁸F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [¹⁸F]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.

SUBMITTER: Lesniak WG

PROVIDER: S-EPMC6563393 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Development of [<sup>18</sup>F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

Lesniak Wojciech G WG Mease Ronnie C RC Chatterjee Samit S Kumar Dhiraj D Lisok Ala A Wharram Bryan B Kalagadda Venkateswara Rao VR Emens Leisha A LA Pomper Martin G MG Nimmagadda Sridhar S

Molecular imaging 20190101

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 [<sup>18</sup>F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12 ...[more]

PMID: 31187691

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Project description:PurposeThe aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection.MethodsTwenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI.Results18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5?±?2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0?±?2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p?<?0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5?±?0.2 compared to 1.3?±?0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7?±?2.3 h), and achieving a consistent final distribution volume averaging 1.4?±?0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57?±?51 min), with an average distribution volume of 3.2?±?1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine.ConclusionTumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

Dataset Information

Development of [¹⁸F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

Publications

Development of [<sup>18</sup>F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

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Dataset Information

Development of [18F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

Publications

Development of [<sup>18</sup>F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Development of [¹⁸F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.