Complexes of technetium-99m with tetrapeptides containing one alanyl and three glycyl moieties

In view of the interesting biological properties of some C-methyl substituted derivatives of 99mTc-MAG3, we have synthesised and evaluated the complexes of 99mTc with tetrapeptides containing three glycyl (G) moieties and one D- or L-alanyl (A) moiety. In mice, 99mTc-L-GAGG, 99mTc-D-GGAG and 99mTc-L-GGAG showed a rapid and high renal excretion, comparable to that of 99mTc-MAG3. Renal handling was somewhat reduced for isomers D and L of 99mTc-AGGG and 99mTc-D-GAGG and markedly inferior for 99mTc-L-GGGA and 99mTc-D-GGGA. In the baboon, 99mTc-L-AGGG, 99mTc-D-AGGG and 99mTc-L-GAGG showed a comparable or even higher 1-h plasma clearance than 99mTc-MAG3. 99mTc-D-GAGG, 99mTc-L-GGAG and 99mTc-D-GGAG were characterised by a lower plasma clearance and the clearance of 99mTc-L-GGGA and 99mTc-D-GGGA was remarkably low. The three 99mTc-labelled tetrapeptides with the highest plasma clearance in a baboon were compared with 99mTc-MAG3 in a human volunteer. 99mTc-L-AGGG and 99m-L-GAGG had a roughly similar plasma clearance as 99mTc-MAG3. The clearance of 99mTc-D-AGGG was significantly lower and liver uptake was clearly visible with this compound. Left kidney renograms of 99mTc-L-AGGG and 99mTc-D-AGGG indicated moderate kidney accumulation. On the other hand, the renogram obtained after injection of 99mTc-L-GAGG had an excellent shape and the maximum kidney concentration was slightly higher than for 99mTc-MAG3. These results show the importance of the position of the methyl substituent on the 99mTc-tetrapeptide with respect to its biological behaviour. (orig./MG)