Page 31 - TPIS2022

Lecture title:

Molecular Imaging with Positron Emission Tomography for Drug
Development in Pulmonary Fibrosis

ABSTRACT:

Purpose/Background
The expression of integrin αvβ6 is increased during fibrogenesis and promotes TGF-β
activation in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), a devastating
lung disease. Detection of αvβ6 integrin receptors can be imaged by positron emission
tomography (PET) with the novel anti-αvβ6 cystine knot peptide (“knottin”) radiotracer,
[18F]FP-R01-MG-F2 (Kimura RH et al, Nat. Comm. 2019). PLN-74809 is an oral,
dual-selective inhibitor of integrins αvβ6 and αvβ1 undergoing clinical trial for the
treatment of IPF. The aim of this study was to evaluate the αvβ6 receptor occupancy
of PLN-74809, as assessed by changes in [18F]FP-R01-MG-F2 uptake following
administration of a single PLN-74809 dose.
Methods
Four IPF patients received a single dose of 60 mg, 120 mg, 240 mg, or 320 mg of PLN-74809.
Dynamic knottin PET images (60 min) were acquired at baseline before treatment and after
a PLN-74809 drug dose one-week later. The uptake kinetics of the knottin radiotracer were
compared pre and post-drug dose in the IPF lung to assess target engagement.
Results
All participants achieved >50% target engagement of αvβ6 receptors in the lungs in a
dose-dependent manner. Moreover, receptor occupancy of αvβ6 approached near
saturation levels (>90%) in two participants at the two highest drug doses administered (240
and 320 mg). No adverse events related to PLN-74809 were reported for the doses given.
Conclusion
PLN-74809 achieved a dose-dependent target engagement of up to 98% in the lungs of IPF
patients. These preliminary data provide insights into the potential mechanism and clinical
benefits of PLN-74809 as an anti-fibrotic therapeutic for this serious lung disease.

5 International TPCF Preclinical Imaging Symposium (2022) 31
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