Formulation of Tc and Re carbonyl complexes using stannous ion as the reductant for pertechnetate and perrhenate

Abstract

The invention relates to novel aminocarboxylate ligands that are suitable for complexing with a radionuclide, and are useful as therapeutic agents and as imaging agents for diagnostic purposes. In accordance with the present invention, a method of preparing a compound of formula fac-[M(CO)3(OH2)3]+  (I) where M is MN, 99mTc, 186Re or 188Re, involves reacting a metal in permetallate form with carbon monoxide and stannous ion. The compound of formula (I) can be reacted with a ligand Lx to form a compound of the formula fac-[M(CO)3Lx]n  (II) wherein M is as defined above, Lx is a monodentate or multidentate ligand or a mixture of these ligands, and n is a charge of the ligand Lx increased with one+charge. The invention also is directed to novel compounds, and kits for carrying out the disclosed methods.

Description

[0001] This application is a continuation of prior co-pending application U.S. Ser. No. 10 / 053,612, filed Jan. 24, 2002, which is a divisional of prior co-pending application U.S. Ser. No. 09 / 576,960, filed May 24, 2000, now U.S. Pat. No. 6,359,119. The entire contents of both of these applications are hereby incorporated by reference.FIELD OF THE INVENTION [0002] The present invention relates to a novel method for preparing Mn, Tc and Re carbonyl complexes which are useful such as for imaging and therapeutic agents. BACKGROUND OF THE INVENTION [0003] Scintigraphic imaging and similar radiographic techniques for visualizing tissues in vivo are finding ever-increasing application in biological and medical research and in diagnostic and therapeutic procedures. Generally, scintigraphic procedures involve the preparation of radioactive agents which, upon introduction to a biological subject, become localized in the specific organ, tissue or skeletal structure of choice. When so localize...

AI Technical Summary

Benefits of technology

The present invention provides a method for preparing a compound of formula (I) by reacting a metal in permanganate form with carbon monoxide and a reducing agent, wherein the reducing agent comprises stannous ion. The compound of formula (I) can be reacted with a ligand Lx to form a compound of the formula (II) wherein M is Mn, 99mTc, 186Re or 188Re, Lx is a monodentate or multidentate ligand or a mixture of these ligands, and n is a charge of the ligand Lx increased with one+charge. The invention also provides a kit for carrying out the method. The technical effect of the invention is to provide a simple and efficient method for preparing a compound of formula (I) which can be further reacted with a ligand Lx to form a compound of formula (II) wherein M is Mn, 99mTc, 186Re or 188Re, Lx is a monodentate or multidentate ligand or a mixture of these ligands, and n is a charge of the ligand Lx increased with one+charge.

Problems solved by technology

Another problem is that technetium-containing scintigraphic imaging agents are known to be unstable in the presence of oxygen, primarily since oxidation of the reductant and / or the technetium-99m destroys the reduced technetium-99m / targeting carrier complex.

For some purposes a problem with using histidine and other unsaturated organic molecules as chelates is that the resulting labeled compound is highly lipophilic resulting in high liver and blood uptake.

The predominant hepatobiliary uptake and clearance are for some purposes undesirable characteristics for the targeted imaging agents.