Synthesis of S‐thiomethyl MAG₃, radiolabelling with technetium‐99m and biological evaluation

Abstract

Protection of the thiolate function of the mercaptoacetyltriglycine (MAG 3 ) by S-thiomethyl group allows automatic deprotection of the protecting group during technetium-99m radiolabelling by transchelation using stannous chloride dihydrate as reductant. Protection of the thiolate group with S-thiomethyl increases the stability of the ligand, desired complex of high radiochemical purity could be prepared under relatively mild labelling condition (at room temperature) omitting the aeration step. The complex prepared from the S-thiomethyl protected MAG 3 ligand were chromatographically (HPLC) and biologically compared with the corresponding complex prepared from the S-benzoylated MAG 3 precursor. This result suggests that technetium-99m complex of MAG 3 could be prepared from S-thiomethylated MAG 3 precursor in comparatively higher purity under relatively milder labelling condition and this method of radiolabelling could be used for the development of less cumbrous single vial MAG 3 kit. Liver1.50 AE 0.26 (2.25 AE 0.31) 4.76 AE 1.72 (4.33 AE 1.34) 2.99 AE 0.79 (2.91 AE 1.24) 4.15 AE 2.42 (4.44 AE 1.55) Intestine 2.29 AE0.44 (2.23 AE 0.33) 2.69 AE 0.58 (2.05 AE 0.16) 3.87 AE 0.84 (3.62 AE 0.59) 2.75 AE 1.93 (2.66 AE 1.64) Kidney 3.07 AE 0.85 (2.48 AE 0.74) 5.47 AE 0.85 (5.32 AE 1.75) 3.21 AE 0.78 (2.53 AE 0.75) 6.73 AE 2.05 (5.39 AE 1.54) Urine 51.92 AE 1.94 (61.03 AE 2.32) 40.52 AE 1.78 (51.21 AE 0.64) 48.87 AE 1.45 (59.95 AE 2.79) 37.64 AE 2.55 (50.24 AE 2.03)Results are expressed as mean AE SD of six mice. In the control set, radiopharmaceuticals were injected to the animals not treated with probenecid.K. Sanyal et al.