Methods and apparatus for synthesizing imaging agents, and intermediates thereof

Abstract

The present invention generally relates to methods and system for the synthesis of imaging agents, and precursors thereof. The methods may exhibit improved yields and may allow for the large-scale synthesis of imaging agents, including imaging agents comprising a radioisotope (e.g., 18F). Various embodiments of the invention may be useful as sensors, diagnostic tools, and the like. In some cases, methods for evaluating perfusion, including myocardial perfusion, are provided. Synthetic methods of the invention have also been incorporated into an automated synthesis unit to prepare and purify imaging agents that comprise a radioisotope. In some embodiments, the present invention provides a novel methods and systems comprising imaging agent 1, including methods of imaging in a subject comprising administering a composition comprising imaging agent 1 to a subject by injection, infusion, or any other known method, and imaging the area of the subject wherein the event of interest is located.

1 - 140 . (canceled) 
     
     
         141 . A syringe comprising a composition comprising the imaging agent comprising the formula: 
       
         
           
           
               
               
           
         
         wherein the syringe adsorbs less than 20% of the imaging agent. 
       
     
     
         142 . The syringe of  claim 141 , wherein the syringe comprises a plunger that adsorbs less than 20% of the imaging agent. 
     
     
         143 . The syringe of  claim 142 , wherein the plunger is not rubber-tipped. 
     
     
         144 . The syringe of  claim 141 , wherein the syringe further comprises sodium ascorbate, ethanol, and water. 
     
     
         145 . The syringe of  claim 142 , wherein the imaging agent is in a solution comprising less than 4% ethanol and less than 50 mg/mL sodium ascorbate in water. 
     
     
         146 . The syringe of  claim 141 , wherein the imaging agent in the syringe is between about 1.5 and about 14 mCi. 
     
     
         147 . The syringe of  claim 141 , wherein the syringe comprises no rubber, and no silicon lubricants. 
     
     
         148 . The syringe of  claim 141 , wherein the syringe is a non-reactive syringe. 
     
     
         149 . The syringe of  claim 142 , wherein the syringe adsorbs between about 1% and about 20%, or between about 5% and about 15%, or between about 1% and about 15%, or between 2% and about 10%, or between about 5% and about 20%. 
     
     
         150 - 156 . (canceled) 
     
     
         157 . An apparatus for synthesizing an imaging agent comprising a linear arrangement of a plurality of stopcock manifolds connected to one or more of the components selected from the group consisting of a [ 18 O]H 2 O recovery system, gas inlet, reservoir with solution of imaging agent precursor, vial, anion exchange cartridge, C-18 cartridge, syringe, solvent reservoir, reaction vessel, collection vessel, reservoir for solution of ascorbic acid or salt thereof, and exhaust outlet. 
     
     
         158 . The apparatus of  claim 157 , further comprising tubing. 
     
     
         159 . The apparatus of  claim 158 , further comprising an imaging agent synthesis module, wherein the apparatus is fluidically connected to the apparatus. 
     
     
         160 . The apparatus of  claim 159 , wherein the apparatus is capable of carrying out the method of claim  74 . 
     
     
         161 . The apparatus of  claim 157 , wherein the apparatus is capable of preparing an imaging agent comprising the formula: 
       
         
           
           
               
               
           
         
       
     
     
         162 . The apparatus of  claim 157 , with the components arranged as shown in  FIG. 8 . 
     
     
         163 . The apparatus of  claim 157 , comprising components arranged in the order: (1) gas inlet; (2) [ 18 O]H 2 O recovery system; (3) anion exchange cartridge; (4) MeCN reservoir; (5) syringe; (6) reservoir with solution of imaging agent precursor; (7) reaction vessel; (8) HPLC system; (9) reservoir with solution of ascorbic acid or a salt thereof; (10) collection vessel; (11) ethanol reservoir; (12) vial with final product; (13) Sep-pack cartridge; (14) reservoir with solution of ascorbic acid or a salt thereof; (15) reaction vessel; and (16) exhaust outlet. 
     
     
         164 . The syringe of  claim 142 , wherein the plunger is rubber-tipped. 
     
     
         165 . The apparatus of  claim 157 , further comprising an HPLC system. 
     
     
         166 . The syringe of  claim 141 , wherein the syringe adsorbs less than 10% of the imaging agent. 
     
     
         167 . The syringe of  claim 142 , wherein the syringe comprises a plunger that adsorbs less than 10% of the imaging agent.