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Improved radiometal complex compositions

A technology of metal complexes and radiopharmaceuticals, applied in the directions of radioactive physical shapes, radioactive carriers, radioactive preparations in vivo, etc., can solve the problem of undisclosed use of radioprotectants.

Active Publication Date: 2006-05-03
GE HEALTHCARE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The kit is briefly disclosed, however, the use of radioprotectants is not disclosed

Method used

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  • Improved radiometal complex compositions
  • Improved radiometal complex compositions
  • Improved radiometal complex compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0015] In a first embodiment, the present invention provides a stabilized composition comprising:

[0016] (i) a metal complex of a radioisotope of technetium or rhenium chelated to a conjugate, wherein the conjugate comprises a tetradentate chelator conjugated to tropane, and the tetradentate The chelating agent forms a neutral metal complex with the radioisotope of technetium or rhenium;

[0017] (ii) at least one radioprotectant.

[0018] The term "tropane" has its conventional meaning, i.e. a bicyclic amine having the following structural formula (ring position numbering shown):

[0019]

[0020] Wherein, the amine nitrogen at the No. 8 position can be a secondary amine or a tertiary amine.

[0021] The term "metal complex" means a coordination complex of a technetium or rhenium metal ion with a ligand, here a tetradentate chelator. The chelated metal complexes are "reverse-chelation resistant", ie not prone to ligand exchange with other potential competing ligands f...

Embodiment 3

[0126] Example 3 studied different 99m Effect of Tc Generator Elution Profile on Performance of Kit Formulations P and Q. 99m The Tc generator was designed to be used for several days, and depending on the age of the generator, and the time since the last elution, various characteristics of the eluate from the elution were obtained. Commercial kits must be able to provide satisfactory RCP preparations under the wide variety of storage and elution conditions used by consumers. Example 3 investigated four sets of elution conditions ("Elution Conditions 1-4). The results showed that these two formulations provided acceptable (92% and 88% for P and Q, respectively). Formulation P had an RCP of 90% 3.5 hours after preparation, while for formulation Q (prior art) RCP in the same time This dropped sharply to 77%.The above results show that Formulation P has improved initial RCP and improved post-manufacturing stability.

[0127] Formulation P had an RCP of 92% shortly after prepar...

Embodiment 4

[0130] Example 4 shows that p-ABA is also 99m Potent radioprotectant of Tc-TRODAT-1 formulations. Addition of p-ABA resulted in a significant increase in RCP. Increasing the level of p-ABA from 200 to 500 μg further improved onset and 4-hour stability.

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Abstract

The present invention relates to stabilised technetium and rhenium metal complex compositions comprising a radioprotectant and a radiometal complex of a tropane-tetradentate chelating agent conjugate, wherein the radiometal complex is neutral. Radiopharmaceuticals comprising the stabilised metal complex compositions, and kits for the preparation of the radiopharmaceuticals are also described.

Description

field of invention [0001] The present invention relates to stabilized technetium and rhenium metal complex compositions comprising a radioprotectant and a radiometal complex of a tropane-tetradentate chelator conjugate, wherein the radiometal complex is neutral. Also disclosed are radiopharmaceuticals comprising the stabilized metal complex compositions, and kits for preparing the radiopharmaceuticals. Background of the invention [0002] use 123 I, 18 F, or 99m Tc-labeled tropane is a known diagnostic imaging radiopharmaceutical for brain imaging [Morgan and Nowotnik, Drug News Perspect. 12(3), 137-145 (1999)]. Tropanes are known to target the dopamine transporter in the brain, and the dopamine transporter is associated with several diseases, including Parkinson's disease, Parkinson's syndrome, and attention deficit hyperactivity disorder. [0003] use 99m Tc-labeled tropanes are known. 99m The development of Tc-TRODAT-1 has been disclosed by Kung [Nucl. Med. Biol., ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/04A61K49/00A61K51/12C07D451/02
CPCA61K51/0497C07D451/02A61K51/04A61K51/12A61K49/00
Inventor D·麦吉尔I·亨里克森
Owner GE HEALTHCARE LTD
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