Automated purification and formulation device for radiopharmaceutical compounds

Patent metadata

Field	Value
Publication number	US-10589250-B2
Application number	US-201715698350-A
Country	US
Kind code	B2
Filing date	Sep 7, 2017
Priority date	Sep 7, 2016
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

A device for purifying and formulating a radiopharmaceutical compound includes an automated purification subsystem that automates the loading of a sample into a sample loop for downstream purification via HPLC. A column selector valve is provided to select from one of a plurality of columns. Fractions can be collected as well as the desired product. The device includes an automated formulation subsystem that first sends the product to a dilution reservoir prior to being pneumatically pushed onto a solid phase extraction (SPE) cartridge. Automated rinse, elution, and reconstitution are also performed with the automated formulation subsystem. The device may be directly coupled to the output of an automated radiosynthesizer.

First claim

What is claimed is:

1. A device for purifying and formulating a radiopharmaceutical compound comprising:
an automated purification subsystem comprising
a computer controlled injection valve coupled to a high performance liquid chromatography (HPLC) pump, a plurality of sample loops, and an output line from the injection valve, the computer controlled injection valve having one or more ports configured to receive an input fluid containing the radiopharmaceutical compound, wherein one of the plurality of sample loops is connected to the HPLC pump and the output line from the injection valve and another sample loop of the plurality of sample loops is connected to a port configured to receive the input fluid;
an automated column selector valve coupled to the output line from the injection valve and configured to select one of a plurality of columns for fluid to pass through;
one or more detectors configured to receive an output of the selected column, the one or more detectors comprising at least a radiation detector;
a downstream fraction selector valve disposed downstream with respect to the one or more detectors and configured to divert fluid flow to one of a product output, waste output, and fraction output; and

an automated formulation subsystem coupled to the product output of the downstream fraction selector valve, the automated formulation subsystem comprising:
a dilution reservoir pre-loaded or filled with a volume of dilution solvent and configured to receive a product fraction from the downstream fraction selector valve, the dilution reservoir fluidically coupled to a solid-phase extraction cartridge;
a computer controlled pump coupled to a plurality of different fluid reagents that include a wash solution, a saline solution, and an eluting solution, the computer controlled pump configured to pump selected fluid reagents through the solid-phase extraction cartridge via a computer controlled cartridge valve interposed between the dilution reservoir and the solid-phase extraction cartridge; and
a final output line fluidically coupled to an output of the solid-phase extraction cartridge, wherein a computer controlled waste valve is coupled to the final output line to divert fluid flow to waste or the final output line; and
a computer accessible controller interfacing with the automated purification subsystem and the automated formulation subsystem, wherein one or more operations of the automated purification subsystem and the automated formulation subsystem, and the controller are programmable by a user.

2. The device of claim 1 , further comprising a final product container, wherein the final output line is coupled to the final product container.

3. The device of claim 1 , wherein the final output line or an output line from the fraction selector valve is coupled to radiosynthesizer device.

4. The device of claim 1 , wherein the computer controlled injection valve comprises a two-position valve, and wherein in a first position, a first sample loop is connected to the HPLC pump and the output line from the injection valve and a second sample loop is connected to the port configured to receive the input fluid, and wherein in a second position the second sample loop is connected to the HPLC pump and the output line from the injection valve and the first sample loop is connected to the port configured to receive the input fluid.

5. The device of claim 1 , wherein the plurality of columns are mounted in respective column holders in the device.

6. The device of claim 1 , wherein the one or more detectors comprise a UV detector and a radiation detector.

7. The device of claim 1 , further comprising a camera positioned to obtain live images of the dilution reservoir.

8. The device of claim 1 , wherein the computer controlled pump coupled to a plurality of different fluid reagents comprises a multi-port syringe pump.

9. The device of claim 1 , further comprising a compressed source of inert gas, the compressed source of inert gas fluidically coupled to the dilution reservoir via an automated valve, wherein the compressed source of inert gas pushes fluid contained in the dilution reservoir into the solid-phase extraction cartridge.

10. The device of claim 1 , wherein the computer accessible controller controls one or more of the injection valve, the HPLC pump, the column selector valve, the downstream fraction selector valve, the pump coupled to a plurality of different fluid reagents, the cartridge valve, and the waste valve.

11. The device of claim 10 , wherein the controller is programmed to automatically actuate a downstream fraction selector valve based on readings obtained from the one or more detectors.

12. The device of claim 11 , wherein the controller is programmed to automatically actuate the downstream fraction selector valve to collect a compound in either the fraction output or product output based on automated peak detection based on designated time windows and/or set threshold values for the one or more detectors.

13. A system for the formation, purification, and formulation of a radiopharmaceutical compound comprising:
a radiosynthesizer device configured for synthesizing radiopharmaceutical compound;
an automated purification subsystem comprising
a computer controlled injection valve coupled to a high performance liquid chromatography (HPLC) pump, one or more sample loops, and an output line from the injection valve, the computer controlled injection valve having one or more ports configured to receive an input fluid containing the radiopharmaceutical compound from the radiosynthesizer device, wherein one of sample loops is connected to the HPLC pump and the output line from the injection valve;
an automated column selector valve coupled to the output line from the injection valve and configured to select one of a plurality of columns for fluid to pass through;
one or more detectors configured to receive an output of the selected column, the one or more detectors comprising at least a radiation detector;
a downstream fraction selector valve disposed downstream with respect to the one or more detectors and configured to divert fluid flow to one of a product output, waste output, and fraction output; and

an automated formulation subsystem coupled to the product output of the downstream fraction selector valve, the automated formulation subsystem comprising:
a dilution reservoir configured to receive a product fraction from the downstream fraction selector valve, the dilution reservoir fluidically coupled to a solid-phase extraction cartridge;
pumping means configured to push fluid contents contained in the dilution reservoir into the solid-phase extraction cartridge in response to actuation of the automated valve;
a computer controlled pump coupled to a plurality of different fluid reagents and configured to pump selected fluid reagents through the solid-phase extraction cartridge via a computer controlled cartridge valve interposed between the dilution reservoir and the solid-phase extraction cartridge;
a final output line fluidically coupled to an output of the solid-phase extraction cartridge, wherein a computer controlled waste valve is coupled to the final output line to divert fluid flow to waste or the final output line; and

a computer accessible controller interfacing with the radiosynthesizer device, the automated purification subsystem, and the automated formulation subsystem, wherein one or more operations of the automated purification subsystem, the automated formulation subsystem, and the controller are programmable by a user.

14. The system of claim 13 , wherein the controller is programmable u

Assignees

• Univ California
• Sofie Biosciences Inc

Inventors

• Schopf Eric
• Moore Melissa
• Van Dam R Michael
• Maraglia Brandon
• Hsiao Alexander

Classifications

• G21G4/08

  specially adapted for medical application (radiation therapy using radioactive sources A61N5/10) · CPC title

• B01J19/004 Primary

  Multifunctional apparatus for automatic manufacturing of various chemical products (sequential reactions B01J19/0046) · CPC title

• G21F7/04

  Shielded glove-boxes (glove-boxes in general B25J21/02) · CPC title

• B01J2219/00164

  controlling the flow · CPC title

• B01J2219/00191

  Control algorithm · CPC title