The discovery and evaluation of [18F]BMS-986229, a novel macrocyclic peptide PET radioligand for the measurement of PD-L1 expression and in-vivo PD-L1 target engagement.
Eur J Nucl Med Mol Imaging
; 51(4): 978-990, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38049658
ABSTRACT
PURPOSE:
A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1.METHODS:
[18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression.RESULTS:
Autoradiography showed an 81 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%.CONCLUSION:
A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombinant Proteins
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Fluorine Radioisotopes
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Carcinoma, Non-Small-Cell Lung
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Fibronectin Type III Domain
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Lung Neoplasms
Limits:
Animals
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Humans
Language:
En
Journal:
Eur J Nucl Med Mol Imaging
Journal subject:
MEDICINA NUCLEAR
Year:
2024
Type:
Article
Affiliation country:
United States