In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1.
Mol Imaging Biol
; 23(2): 241-249, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33098025
ABSTRACT
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 [18F]AlF-NOTA-ZPD-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 ZPD-L1_4, to determine if improved affinity for PD-L1 resulted in increased in vivo targeting of PD-L1. PROCEDURES ZPD-L1_4 was conjugated with NOTA and radiolabeled with either [18F]AlF or 68Ga. [18F]AlF-NOTA-ZPD-L1_4 and [68Ga]NOTA-ZPD-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 ([18F]AlF-NOTA-ZPD-L1_4 LOX 8.7 ± 0.7 %ID/g (N = 4) SUDHL6 0.2 ± 0.01 %ID/g (N = 6), [68Ga]NOTA-ZPD-L1_4 LOX 15.8 ± 1.0 %ID/g (N = 6) SUDHL6 0.6 ± 0.1 %ID/g (N = 6)), considerably higher than ZPD-L1_1. In rhesus monkeys, both PET tracers showed fast clearance through kidneys and low background signal in the liver ([18F]AlF-NOTA-ZPD-L1_4 1.26 ± 0.13 SUV, [68Ga]NOTA-ZPD-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:
[18F]AlF-NOTA-ZPD-L1_4 and [68Ga]NOTA-ZPD-L1_4 are promising candidates for same-day clinical PD-L1 PET imaging, warranting clinical evaluation. The ability to use either [18F] or [68Ga] may expand access to clinical sites.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiometria
/
Compostos Radiofarmacêuticos
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Tomografia por Emissão de Pósitrons
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Antígeno B7-H1
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Anticorpos Monoclonais
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Neoplasias
Tipo de estudo:
Evaluation_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Imaging Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos