Type 2 diabetes is a disease in which the pancreas does not produce enough insulin to regulate the level of glucose in the blood or the body is unable to use the insulin produced effectively. This leads to high blood glucose levels and other complications. Canagliflozin blocks a protein in the kidneys called sodium-glucose cotransporter 2 (SGLT2). When the blood is filtered in the kidneys, SGLT2 absorbs glucose from the urine and releases it back into the bloodstream. By blocking the action of SGLT2, Canagliflozin increases the excretion of glucose in the urine, lowering blood glucose levels (EMA/302887/2020). SGLT2 inhibitors also reduce the risk of cardiovascular and renal disease in patients with and without type 2 diabetes, albeit with great inter-individual variation.
The underlying mechanisms for this variation in response could be attributed to differences in SGLT2 occupancy, due to individual variation in plasma and tissue drug exposure and receptor availability.
To gain a better understanding of the underlying mechanisms, together with the UMCG Symeres has worked on the development of a labeled version of this SGLT2 inhibitor, namely [18F]-Canagliflozin (link to PET web page). This made it possible to track this drug in the body after injection using Positron Emission Tomography (PET). We investigated whether [18F]Canagliflozin PET imaging can be used to determine Canagliflozin disposition in tissue and SGLT2 occupancy.
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