The present invention relates to an improved process for the preparation of macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to the process for the preparation of metal complexes of macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1) with purity greater than 99.0% by HPLC. The present invention also relates to an improved process for the preparation of gadolinium complex of formula (1a) with macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to a novel process for the preparation of calcium complex of formula (1b) with macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1).

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The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

Disclosed is a method for producing calcobutrol used as an MRI contrast agent. The method comprises the steps of: obtaining butrol represented by chemical formula 2 in the specification by reacting a gadobutrol represented by chemical formula 1 in the specification and a decomplexing agent; and obtaining a calcobutrol represented by chemical Formula 3 in the specification by reacting butrol with calcium ions.

Disclosed is a method for producing calcobutrol used as an MRI contrast agent. The method comprises the steps of: obtaining butrol represented by chemical formula 2 in the specification by reacting a gadobutrol represented by chemical formula 1 in the specification and a decomplexing agent; and obtaining a calcobutrol represented by chemical Formula 3 in the specification by reacting butrol with calcium ions.

The invention relates to a marking precursor incorporating a chelator or fluorination group for radiolabelling with 44Sc, 47Sc, 55Co, 62Cu, 64Cu, 67Cu, 66Ga, 67Ga, 68Ga, 89Zr, 86Y, 90Y, 90Nb, 99mTc, 111ln, 135Sm, 140Pr, 159Gd, 149Tb, 160Tb, 161Tb, 165Er, 166Dy, 166Ho, 175Yb, 177Lu, 186Re, 188Re, 213Bi and 225Ac or with 18F, 131I or 211At, and one or two biological targeting vectors which are coupled to the chelator or fluorinating group via one or more squaric acid groups.

Conjugates of an active agent attached to a targeting moiety, such as at least one HSP90 binding moiety, via a linker, have been designed. Such conjugates can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.

The present invention relates to the preparation of a series of chiral DOTA, DO3A, DO2A, DO1A, cyclen and their metal complexes, which display properties superior to those of previous DOTA-based compounds, and hence are potentially valuable as a platform for diagnostic applications. The chiral DOTAs reveal a high abundance of twisted square antiprism (TSA) geometry favoring them to be used as potential MRI contrast agents, whereas their rapid labelling properties at mild conditions make them excellent candidates for use as radiometal chelators.

The present invention relates to the preparation of a series of chiral DOTA, DO3A, DO2A, DO1A, cyclen and their metal complexes, which display properties superior to those of previous DOTA-based compounds, and hence are potentially valuable as a platform for diagnostic applications. The chiral DOTAs reveal a high abundance of twisted square antiprism (TSA) geometry favoring them to be used as potential MRI contrast agents, whereas their rapid labelling properties at mild conditions make them excellent candidates for use as radiometal chelators.

Disclosed are chelates resulting from the complexation of bifunctional do2pa derivatives ligands of formula (I), wherein the substituents R.sup.1, R.sup.1′, R.sup.2, R.sup.2′, R.sup.3, R.sup.3′, L.sup.1, L.sup.1′, L.sup.2 and L.sup.2′ are defined as in the claims, with metallic cations, especially Pb(II) and Bi(III). Also disclosed are bifunctional do2pa derivatives ligands of formula (I), as well as the use of chelates in nuclear medicine and the use of ligands in cations detection or epuration of effluents.

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