99mTc-labelled biguanide derivatives: chemical speciation modelling thereof and evaluation in vervets

Abstract

99mTc-DMSA (dimercaptosuccinic acid) is known to be a safe and effective agent for static renal imaging. However, it has a long uptake time which is a limiting factor in diagnostic procedures and also leads to a relatively high radiation dose being administered to patients. There is a constant search for possible new renal imaging agents with a good resolution, kidney/liver contrast and low radiation dose to all organs. A series of biguanide derivatives (potential as noninsulin-dependent diabetes mellitus agents) labelled with 99m Tc were investigated as potential alternative kidney-imaging agents on theoretical grounds (in silico) and their biodistribution (in vivo) verified in a limited number of animal experiments. Such a dual approach has the benefit that it reduces the number of animal experiments needed to evaluate a potential radiopharmaceutical. The blood plasma model shows little or no complexation of the biguanide type ligands by the metal ions in blood plasma. It was therefore expected that these ligands will clear rapidly through the kidneys and liver (increased lipophilicity). These predictions were verified by studies on single vervets comparing them with Tc-CBIG (carboxylbiguanide) has a very fast kidney clearance, which will reduce the dose to organs (as experienced for 99m Tc-DMSA), although it's potential as a kidney agent is limited by its gallbladder uptake.