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After repeated intravenous administration in rats, gadoteridol was 10 times less retained than gadodiamide, and all of the detected gadolinium was in the form of intact soluble gadolinium complex; exposure to gadodiamide resulted in retention of both soluble and insoluble gadolinium-containing species, with insoluble materials dominating.

Two probes consisting of vitamin B12(CNCbl) conjugated to Gd chelates by esterification of the ribose 5′‐OH moiety, Gd–DTPA–CNCbl (1; DTPA=diethylenetriamine‐N,N,N′,N′′,N′′‐pentaacetic acid) and Gd–TTHA–CNCbl (2; TTHA=triethylenetetramine‐N,N,N′,N′′,N′′′,N′′′‐hexaacetic acid), have been synthesised and characterised. The crystal structure of a dimeric form of 1, obtained by crystallisation with an excess of GdCl3, has been determined. The kinetics of binding to and dissociation from transcobalamin II show that 1and 2maintain high‐affinity binding to the vitamin B12transport protein. Complex 2is very stable with respect to Gd3+release owing to the saturated co‐ordination of the Gd3+ion by four amino and five carboxylate groups. Hydrolysis of the ester functionality occurs on the time scale of several hours. The lack of saturation and the possible involvement of the ester functionality in co‐ordination result in lower stability of 1towards hydrolysis and in a considerable release of Gd3+in vitro. Gd3+ions released from 1are avidly taken up by the K562 tumour cells to an extent corresponding to approximately 1010Gd3+per cell. The internalisation of toxic Gd3+ions causes a marked decrease in cell viability as assessed by Trypan blue and WST‐1 tests. On the contrary, the experiments with the more stable 2did not show any significant cell internalisation of Gd3+ions and any influence on cell viability. The results point to new avenues of in situ generation of cytotoxic pathways based on the release of toxic Gd3+ions by vitamin B12bioconjugates.

The synthesis of a group of 2-methylimidazo[1,2-a]pyrimidine-3-carboxylic esters, acids and amides is described. The structures of new compounds are supported by 1H and 13C NMR spectra. These compounds were tested in vivo for their antiinflammatory, analgesic and ulcerogenic activity. Eight new compounds out of fifteenshowed remarkable dose-dependent antiinflammatory action in the carrageenan rat paw edema (1/2–1/3 × indomethacin) but weak analgesic activity in the acetic acid writhing test together with negligible ulcerogenic action. The new compounds were found to be lacking in inhibitory activity on cyclooxygenase in vitro.

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