Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule

Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-RESCA method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the restrained complexing agent (RESCA) chelator for direct labeling with [18F]Al-F. In vivo PET/MRI scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, for PDGFRβ, with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer's high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value (SUV) 0.43±0.05), with uptake decreasing during recovery (SUV 0.29±0.03) (p<0.0001). [18F]AlF-RESCA-Z09591 accurately detects PDGFRβ, offering non-invasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.