Radiopharmaceutical products

Abstract

The present invention relates to improved radiopharmaceutical compositions in sealed containers, where the container closure has an ETFE (ethylene-tetrafluoroethylene copolymer) coating. Also disclosed are kits for radiopharmaceutical preparation using the sealed containers, as well as methods of preparation of radiopharmaceuticals using the sealed containers.

1 - 28 . (canceled) 
     
     
         29 . A method for imaging, which comprises
 (i) reaction of a synthetic ligand and a radioisotope composition, wherein the synthetic ligand comprises one or more phosphine, thiol or isonitrile metal-binding groups,
 the synthetic ligand composition comprising:
 (a) a synthetic ligand precursor, 
 (b) an optional radioprotectant selected from ascorbic acid or a salt thereof with a biocompatible cation; 
 (c) a biocompatible reductant that comprises stannous ion; and 
 (d) an effective amount of a pH-adjusting agent that is sodium 
 
 bicarbonate, sodium hydrogen carbonate, or a combination thereof; and 
 the radioisotope composition comprising radioisotope capable of reacting with the synthetic ligand; and 
   (ii) puncturing a pre-treated closure of a container that contains the product of the reaction in step (i) with a hypodermic needle while maintaining sealed integrity, the pre-treated closure comprising a chlorinated butyl rubber body which is coated with ethylene-tetrafluoroethylene copolymer (ETFE) on one or more of its surface(s) which are in contact with the container contents.   
     
     
         30 . The method of  claim 29 , where the reaction of (i) and (ii) is carried out within the sealed container. 
     
     
         31 . The method of  claim 29 , where the radioisotope is a positron emitter and the reaction and/or transfer of reaction product is carried out using an automated synthesizer apparatus. 
     
     
         32 . The method of  claim 29 , where the precursor is supplied as a kit. 
     
     
         33 . The method of  claim 29 , where the chlorinated butyl rubber body is laminated onto the closure. 
     
     
         34 . The method of  claim 29 , where the coating covers all surfaces of the closure except those which form the sealing area with the container. 
     
     
         35 . The method of  claim 29 , wherein the closure is pre-treated by heating in a dry oven. 
     
     
         36 . The method of  claim 29 , wherein the closure is pre-treated by heating the closure to remove oxygen gas dissolved within the closure material and/or coating and re-equilibrating the closure under an atmosphere of a chemically unreactive gas. 
     
     
         37 . The method of  claim 29 , where the closure has a single vent igloo shape. 
     
     
         38 . The method of  claim 29 , wherein the synthetic ligand composition consists essentially of about 0.69 mg tetrofosmin, about 90 μg of stannous chloride dihydrate, about 0.96 mg disodium sulfosalicylate, about 3.0 mg sodium D-gluconate, about 5.0 mg ascorbic acid, about 11.0 mg sodium hydrogen carbonate, and a pH on reconstitution of 8.3 to 9.1. 
     
     
         39 . The method of  claim 29 , wherein the synthetic ligand is tetrofosmin.