US 12,235,250 B2
Radiopharmaceutical production system and quality control system utilizing high performance liquid chromatography
Ronald Nutt, Friendsville, TN (US); Anthony M. Giamis, Green Oaks, IL (US); and Aaron McFarland, Knoxville, TN (US)
Assigned to Best ABT, Inc., Springfield, VA (US)
Filed by Ronald Nutt, Friendsville, TN (US); Anthony M. Giamis, Green Oaks, IL (US); and Aaron McFarland, Knoxville, TN (US)
Filed on Apr. 13, 2012, as Appl. No. 13/446,334.
Application 13/446,334 is a continuation in part of application No. 12/565,544, filed on Sep. 23, 2009, granted, now 8,333,952.
Application 13/446,334 is a continuation in part of application No. 12/565,552, filed on Sep. 23, 2009, abandoned.
Prior Publication US 2013/0130309 A1, May 23, 2013
Int. Cl. G01N 30/74 (2006.01); A61K 51/04 (2006.01); B01J 19/00 (2006.01); G01N 30/88 (2006.01); G01N 33/60 (2006.01); G01N 30/00 (2006.01)
CPC G01N 30/74 (2013.01) [A61K 51/0491 (2013.01); B01J 19/0093 (2013.01); G01N 30/88 (2013.01); G01N 33/60 (2013.01); B01J 2219/00788 (2013.01); B01J 2219/00873 (2013.01); B01J 2219/00891 (2013.01); B01J 2219/00905 (2013.01); G01N 2030/77 (2013.01); G01N 2030/8872 (2013.01)] 34 Claims
 
1. An integrated radiopharmaceutical production and quality control testing system, the system comprising:
a cyclotron configured to form a radioisotope in a fluid phase;
a chemical production module in communication with the cyclotron configured to receive the radioisotope in the fluid phase, the chemical production module configured to form a purified radiopharmaceutical solution including the radioisotope;
a quality control module in communication with the chemical production module, the quality control module configured to receive from the chemical production module a sample radiopharmaceutical solution of the purified radiopharmaceutical solution including the radioisotope, the quality control module including:
a pumping mechanism coupled to the chemical production module and configured to receive from the chemical production module the sample radiopharmaceutical solution of the purified radiopharmaceutical solution including the radioisotope, the pumping mechanism configured to separate the sample radiopharmaceutical solution into a first portion, a second portion, and a third portion;
a valve mechanism in downstream communication with the pumping mechanism and configured to selectively receive at least two of the three portions of the sample radiopharmaceutical solution from the pumping mechanism;
wherein said valve mechanism comprises a plurality of input and output valve lines;
wherein said valve mechanism is configured to rotate at a predetermined angle to change configuration from a state A to a state B for selectively directing the at least two of the three portions of the sample radiopharmaceutical solution through different predefined pairs of input and output valve lines;
a light analyzer in communication with the valve mechanism configured to receive the first portion of the sample radiopharmaceutical solution and to determine the optical clarity of the sample radiopharmaceutical solution from the first portion of the sample radiopharmaceutical solution;
a high performance liquid chromatography column in communication with the valve mechanism, the high performance liquid chromatography column configured to receive the first portion of the sample radiopharmaceutical solution and to separate the first portion of the sample radiopharmaceutical solution into a number of separated molecularly distinct species, the high performance liquid chromatography column in downstream communication with the light analyzer;
a mobile phase solvent mechanism in communication with the valve mechanism, the mobile phase solvent mechanism having a mobile phase solvent reservoir configured to store a mobile phase solvent therein to selectively introduce the mobile phase solvent into the high performance liquid chromatography column through the valve mechanism to facilitate separation of the radiopharmaceutical solution into the number of separated molecularly distinct species;
a refractive index analyzer in downstream communication with the high performance liquid chromatography column, the refractive index analyzer configured to receive the separated molecularly distinct species from the high performance liquid chromatography column and to determine the refractive index of and quantify each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the first portion of the sample radiopharmaceutical solution; and
a radiation probe disposed in the quality control module, the radiation probe in communication with the valve mechanism and in upstream and downstream communication with the high performance liquid chromatography column, the radiation probe configured to measure the radioactivity of the first portion of the sample radiopharmaceutical solution upstream of and before the first portion of the sample radiopharmaceutical solution enters the high performance liquid chromatography column and to measure the radioactivity of each of the number of separated molecularly distinct species in the sample radiopharmaceutical solution from the separated molecularly distinct species in the first portion of the sample radiopharmaceutical solution after the separated molecularly distinct species exit downstream of the high performance liquid chromatography column.