Type I collagen–targeted PET probe for pulmonary fibrosis detection and staging in preclinical models

Abstract

Pulmonary fibrosis is a scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe a peptide-based PET probe (68Ga-CBP8) that targets collagen type I. We evaluated 68Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. 68Ga-CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. The lung PET signal and lung 68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2=0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the 68Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that 68Ga-CBP8 is a promising candidate for non-invasive imaging of human pulmonary fibrosis.

Molecular Probes for Imaging Fibrosis and Fibrogenesis

“…68 Ga-CBP8 showed high efficacy for pulmonary fibrosis and high target/background ratios in the standard bleomycin mousem odel of pulmonary fibrosis ( Figure 6D)a nd in the bleomycinm odel of pulmonary fibrosis associated with vascular leak. [80] In both models, the lung PET signal and lung 68 Ga-CBP8 uptake (quantified ex vivo) correlated strongly (r 2 = 0.80) with the collagen concentration in fibrotic mice.…”

“…In-DTPA-A20FMDV2SPECT integrin avb6pulmonary fibrosis [ MRItype Ic ollagen MI, [64,65] myocardial perfusion, [66] liver fibrosis, [67,68] type Ic ollagen pulmonary fibrosis [80]…”

“…[73] C) Structures of the collagen-binding PET probes 64 Cu-CBP7, [77] Al 18 F-CBP9, [79] Al 18 F-CBP10, [79] and 68 Ga-CBP8. [80] 64 Cu-CBP11 [77] and 68 Ga-CBP12 [80] are the nonbindingi somers of 64 Cu-CBP7 and 68 Ga-CBP8, respectively,i nw hich one l-cysteine was replaced by d-cysteine. D) Representativef used PET-CT images of a control and fibrotic mouse,w hich demonstrate that 68 Ga-CBP8/PET can detect bleomycin-induced pulmonary fibrosis.…”

Molecular imaging of fibrosis: recent advances and future directions

“…The same type I collagen-binding peptide was also adapted for PET imaging (45,46). 68 Ga-CBP8 binds type I collagen with low micromolar affinity and is quickly cleared from the circulation into the urine (45).…”

Functional Imaging with Nucleic‐Acid‐Based Sensors: Technology, Application and Future Healthcare Prospects

“…Similarly, radionuclide imaging is facilitated mostly by gene reporter systems and probes . A recent study involved a peptide‐based PET (positron emission tomography) probe for imaging lung fibrosis in mouse models and diseased tissue from patients . Potential development of NA‐based radionuclide and MRI probes could improve disease diagnostic capability through whole‐body multi‐biomarker imaging.…”