Synthesis and Preclinical Evaluation of Ga-68-labeled Adnectin as a PET Agent for Imaging PD-L1 Expression

Robu, Stephanie; Richter, Antonia; Gosmann, Dario; Seidl, Christof; Leung, David; Hayes, Wendy; Morin, Paul E.; Smith, Randall A.; Donelly, DJ; Lipovšek, Daša; Bonacorsi, SJ; Cohen, Daniel N.; Krackhardt, Angela M.; Weber, W.

doi:10.1055/s-0040-1708129

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“…These radiation doses may limit broader use of PD-(L)1 imaging, especially for serial PET scans to monitor changes in PD-(L)1 expression in individual patients. Development of PET imaging agents labeled with short-lived positron emitters, such as 18 F or 68 Ga, is a highly active research field with encouraging preclinical and clinical results ( 12 , 72 , 105 ). PET imaging studies generally use micro-dosing, defined as less than one hundredth of the dose that has a pharmacological effect, to a maximum of 100 µg, which is considered to have a very limited risk to participants ( 106 ).…”

Section: From Preclinical To Clinical Studies Using Pd-(l)1 Pet Tracersmentioning

confidence: 99%

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

et al. 2021

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Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors target the important molecular interplay between PD-1 and PD-L1, a key pathway contributing to immune evasion in the tumor microenvironment (TME). Long-term clinical benefit has been observed in patients receiving PD-(L)1 inhibitors, alone and in combination with other treatments, across multiple tumor types. PD-L1 expression has been associated with response to immune checkpoint inhibitors, and treatment strategies are often guided by immunohistochemistry-based diagnostic tests assessing expression of PD-L1. However, challenges related to the implementation, interpretation, and clinical utility of PD-L1 diagnostic tests have led to an increasing number of preclinical and clinical studies exploring interrogation of the TME by real-time imaging of PD-(L)1 expression by positron emission tomography (PET). PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression spatially and temporally. Several PD-(L)1 PET tracers have been tested in preclinical and clinical studies, with clinical trials in progress to assess their use in a number of cancer types. This review will showcase the development of PD-(L)1 PET tracers from preclinical studies through to clinical use, and will explore the opportunities in drug development and possible future clinical implementation.

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Section: From Preclinical To Clinical Studies Using Pd-(l)1 Pet Tracersmentioning

confidence: 99%