18F and 99mTc labeled bile acid analogues to study (altered) hepatobiliary transporter function

Numerous drugs are substrate or inhibitor of hepatobiliary transport mechanisms. This can lead to drug induced liver injury. Therefore, it is important to assess these possible interactions from early on during drug development.

Figure 1: Overview of the most important bile acid transporters. Organic Anion Transport Protein 1a/1b (Oatp1a/1b), Sodium Taurocholate Cotransporting Protein (NTCP) are the most important uptake transporters. Multidrug Resistance Protein 2 (Mrp2) and Bile Salt Export Pump (Bsep) are the most important efflux transporters

Aim: synthesis of radiolabeled substrates (bile acid analogues) which can be used for molecular SPECT and PET imaging. This is a non-invasive in vivo method to allow visualization and quantification of normal and disturbed hepatobiliary transport. The use of a non-invasive method can significantly reduce the cost for preclinical drug development.

Figure 2: Dynamic USPECTII-CT (MILabs) acquisition of 37 MBq of a technetium labeled bile acid analogue. After injection, the tracer is taken up from the blood into the hepatocytes, and are then transported to the gallbladder and intestine. Additionally, the tracer is cleared by the kidneys. 120 frames; 1 min/frame; 4 bed positions

Researchers: Stef De Lombaerde, Sara Neyt