E!11549 BONIFIB, Development of BOT501, a Non-invasive Imaging Diagnostic for Fibrosis

Purpose and goal

Develop a method for in vivo quantification of PDGFRbeta as a biomarker for ongoing fibrosis with [68Ga]Ga-BOT5035 and PET-CT. Uptake of [68Ga]Ga-BOT5035 in the right atrium in a patient with atrial fibrillation is followed up in a new study in patients with cardiac fibrosis. However, it does not appear possible to detect an ongoing liver fibrosis with [68Ga]Ga-BOT5035. With oxygen water, regional blood flow in the liver can be quantified and the ratio of arterial / venous blood flow calculated. The latter is further studied in a larger patient population with other funding.

Expected results and effects

There are possibilities that [68Ga]Ga-BOT5035 can be used in fibrotic diseases other than liver fibrosis, for example in heart fibrosis. This accidential finding is further studied. Fibrosis development in the liver is likely to occur very slowly over a long period of time and the PDGFRbeta concentration is probably too low to provide significant binding of [68Ga]Ga-BOT5035. Quantification of liver perfusion with oxygen-15 water will be studied in a larger patient population as a method for preoperative assessment prior to liver surgery. A PET-CT study is underway to evaluate this.

Planned approach and implementation

Radiochemistry - synthesis of [68Ga]Ga-BOT5035 preclinical in vitro and in vivo studies with [68Ga]Ga-BOT5035 GMP qualification and validation of production and analysis methods for [68Ga]Ga-BOT5035 Application for a clinical First-In-Man study, IMPD, IB, CSP, EPM. Recrutiment of patients Clinical First-In-Man PET-CT study in patients with liver fibrosis PET data analysis using tracer kinetic modelling