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In Vivo Evaluation ...
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Rubins, Daniel J.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2020-10-23
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Springer,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-438963
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-438963URI
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https://doi.org/10.1007/s11307-020-01544-2DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Purpose: In vivo imaging of programmed death ligand 1 (PD-L1) during immunotherapy could potentially monitor changing PD-L1 expression and PD-L1 expression heterogeneity within and across tumors. Some protein constructs can be used for same-day positron emission tomography (PET) imaging. Previously, we evaluated the PD-L1-targeting Affibody molecule [F-18]AlF-NOTA-Z(PD-L1_1) as a PET tracer in a mouse tumor model of human PD-L1 expression. In this study, we evaluated the affinity-matured Affibody molecule Z(PD-L1_4), to determine if improved affinity for PD-L1 resulted in increased in vivo targeting of PD-L1.Procedures: Z(PD-L1_4) was conjugated with NOTA and radiolabeled with either [F-18]AlF or Ga-68. [F-18]AlF-NOTA-Z(PD-L1_4) and [Ga-68]NOTA-Z(PD-L1_4) were evaluated in immunocompromised mice with LOX (PD-L1+) and SUDHL6 (PD-L1-) tumors with PET and ex vivo biodistribution measurements. In addition, whole-body PET studies were performed in rhesus monkeys to predict human biodistribution in a model with tracer binding to endogenous PD-L1, and to calculate absorbed radiation doses.Results: Ex vivo biodistribution measurements showed that both tracers had > 25 fold higher accumulation in LOX tumors than SUDHL6 ([F-18]AlF-NOTA-Z(PD-L1_4): LOX: 8.7 +/- 0.7 %ID/g (N = 4) SUDHL6: 0.2 +/- 0.01 %ID/g (N = 6), [Ga-68]NOTA-Z(PD-L1_4): LOX: 15.8 +/- 1.0 %ID/g (N = 6) SUDHL6: 0.6 +/- 0.1 %ID/g (N = 6)), considerably higher than Z(PD-L1_1). In rhesus monkeys, both PET tracers showed fast clearance through kidneys and low background signal in the liver ([F-18]AlF-NOTA-Z(PD-L1_4): 1.26 +/- 0.13 SUV, [Ga-68]NOTA-Z(PD-L1_4): 1.11 +/- 0.06 SUV). PD-L1-expressing lymph nodes were visible in PET images, indicating in vivo PD-L1 targeting. Dosimetry estimates suggest that both PET tracers can be used for repeated clinical studies, although high kidney accumulation may limit allowable radioactive doses.Conclusions: [F-18]AlF-NOTA-Z(PD-L1_4) and [Ga-68]NOTA-Z(PD-L1_4) are promising candidates for same-day clinical PD-L1 PET imaging, warranting clinical evaluation. The ability to use either [F-18] or [Ga-68] may expand access to clinical sites.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Meng, XiangjunMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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McQuade, PaulMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Klimas, MichaelMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Getty, KristaMerck & Co Inc, Screening & Prot Sci Dept, West Point, PA USA.
(author)
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Lin, Shu-AnMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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Connolly, Brett M.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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O'Malley, Stacey S.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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Haley, HykingMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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Purcell, MonaMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Gantert, LizaMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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Holahan, MarieMerck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
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Lindgren, JoelAffibody AB, Solna, Sweden.
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Eklund, PärAffibody AB, Solna, Sweden.
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Ekblad, CarolineAffibody AB, Solna, Sweden.
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Frejd, Fredrik Y.Uppsala universitet,Medicinsk strålningsvetenskap,Affibody AB, Solna, Sweden.(Swepub:uu)freni195
(author)
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Hostetler, Eric D.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Gonzalez Trotter, Dinko E.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Evelhoch, Jeffrey L.Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.
(author)
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Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.Merck & Co Inc, Screening & Prot Sci Dept, West Point, PA USA.
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In:Molecular Imaging and Biology: Springer23, s. 241-2491536-16321860-2002
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Rubins, Daniel J ...
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Meng, Xiangjun
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McQuade, Paul
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Klimas, Michael
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Getty, Krista
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Lin, Shu-An
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Connolly, Brett ...
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O'Malley, Stacey ...
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Haley, Hyking
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Purcell, Mona
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Gantert, Liza
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Holahan, Marie
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Lindgren, Joel
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Eklund, Pär
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Ekblad, Caroline
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Frejd, Fredrik Y ...
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Hostetler, Eric ...
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