In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1

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In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1

Rubins, Daniel J. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Meng, Xiangjun (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

McQuade, Paul (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Klimas, Michael (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Getty, Krista (author): Merck & Co Inc, Screening & Prot Sci Dept, West Point, PA USA.

Lin, Shu-An (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Connolly, Brett M. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

O'Malley, Stacey S. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Haley, Hyking (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Purcell, Mona (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Gantert, Liza (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Holahan, Marie (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Lindgren, Joel (author): Affibody AB, Solna, Sweden.

Eklund, Pär (author): Affibody AB, Solna, Sweden.

Ekblad, Caroline (author): Affibody AB, Solna, Sweden.

Frejd, Fredrik Y. (author): Uppsala universitet,Medicinsk strålningsvetenskap,Affibody AB, Solna, Sweden.

Hostetler, Eric D. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Gonzalez Trotter, Dinko E. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

Evelhoch, Jeffrey L. (author): Merck & Co Inc, Translat Biomarkers Dept, West Point, PA 19486 USA.

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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. (creator_code:org_t)

2020-10-23
2021
English.
In: Molecular Imaging and Biology. - : Springer. - 1536-1632 .- 1860-2002. ; 23, s. 241-249

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Keyword

PD-L1
PET
Oncology PET imaging
Molecular imaging
Affibody molecules
Translational research
Oncology biomarker

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