Device and method for performing automated radiochemical purity analysis of PET tracers

Abstract

The present invention relates to a device that enables fully automated radiochemical purity analysis of a radiolabeled solution sample based on a chromatogram obtained by thin-film chromatography (TLC), the device comprising an automated instrument including a disposable TLC strip holder assembly, a radioactivity detector, and a pipette.

Claims

1. A device for performing automated radiochemical purity analysis of a radiolabeled solution sample based on a chromatogram obtained by thin-film chromatography, i.e., TLC, Hereinafter referred to as the holder assembly, the TLC strip holder assembly (20) is as follows: A disposable TLC strip (6) comprising an upper cover (8) and a lower TLC band (9), wherein the lower TLC band (9) is sealed in a sealing area (10) at a first end to the upper cover (8), the other end of the lower TLC band (9) is in the shape of a tapered tip (14) that can be freely separated from the corresponding end of the upper cover (8), the upper cover (8) comprises a first hole or drive hole (11) located at the other end of the upper cover (8), a second hole or eluent hole (12) located above the tapered tip (14) of the lower TLC band (9), and a third hole or spotting hole (13) located above the lower TLC band (9) at a certain distance from the second hole (12), A reusable TLC strip holder (7), hereinafter referred to as a holder, comprising an eluent container (16) positioned below a top surface (15), wherein the TLC strip holder (7) further has an opening (12') for communicating with the eluent container (16), which aligns with the second hole (12) of the upper cover (8) when the TLC strip (6) is fully inserted into the holder, and has a sharply angled guide opening (17) for passing the tapered tip (14) of the lower TLC band (9) downward into the eluent container (16), the tapered tip (14) being separated from the upper cover (8) when the tapered tip (14) is inserted into the eluent container (16), while the remainder of the TLC strip (6) remains guided by a retaining notch (18). A TLC strip holder assembly (20) consisting of, A fixed radioactivity detector (43) is positioned in the same line as the holder (7) and is equipped with a shielding component (44), An automated device (40) comprising a pipette (42) capable of housing disposable pipette ends (41), drawing fluid into or discharging fluid from each pipette end (41), positioning the pipette ends (41) in the spotting hole (13), the eluent hole (12), and the drive hole (11), respectively, distributing spots of a radiolabeled solution sample onto the lower TLC band (9), providing the eluent, also called the mobile phase, to the eluent container (16), and displacing the TLC strip (6) along a guide groove (18) outside the holder (7) toward the fixed radioactivity detector (43), A device equipped with the following features.

2. The device according to claim 1, wherein the upper cover (8) is a transparent plastic sheet, and the lower TLC band (9) of the TLC strip (6) is made of an aluminum or plastic support sheet coated with a stationary phase such as silica gel, C18-modified silica, silica having a chiral selector, alumina, or polyamide, or glass microfiber chromatography paper impregnated with silica gel or cellulose.

3. The device according to claim 1, further comprising an optical system such as a camera capable of identifying the location of the eluent front line along the TLC plate and any visual migration features.

4. The device according to claim 1, wherein the reusable holder (7) further comprises a groove (19) that provides clearance to the end of the drive pipette end (41) while the TLC strip (6) is displaced in or out of the holder (7).

5. The device according to claim 1, wherein the eluent container (16) is designed to accommodate an eluent volume between 200 μL and 600 μL.

6. The device according to claim 2, wherein the plastic upper cover (8) is polyethylene, a cyclic olefin copolymer i.e., COC, or polyethylene terephthalate.

7. A method for performing automated radiochemical purity analysis of a radiolabeled solution sample by TLC using the device described in any one of claims 1 to 6, A step of arranging a holder assembly, wherein in the device according to claim 1, the TLC strip (6) is first positioned in the holder (7) such that the eluent hole (12) coincides with the opening (12') of the eluent container (16), The steps include providing a first tip (41) to the automatic pipette (42) and drawing in a sample of the radiolabeled compound, The first tip (41) is moved within the spotting hole (13) to distribute spots of the radiolabeled compound sample onto the surface of the lower TLC band (9), The steps include discarding the first tip (41), attaching a second tip (41) to the automatic pipette (42), and moving the second tip (41) to draw in a specified amount of eluent from an external supply source, The steps include moving the second tip (41) within the eluent hole (12) and distributing the eluent into the eluent container (16), A step of allowing mobile phase migration to unfold for a certain period of time, enabling sufficient mobile phase migration to correspond to an appropriate eluent front-end position measured and verified by the optical system, The steps include discarding the second tip (41), placing a third tip (41) in the automatic pipette (42), moving the third tip (41) into the drive hole (11), and driving the TLC strip (6) from the holder (7) toward and across the field of view of the fixed radioactivity detector (43) to obtain a chromatogram, wherein the drive speed profile is adapted to the type and activity level of the detector; The steps include analyzing the chromatogram and evaluating the radiochemical purity of the radiolabeled compound. Methods that include...

8. The method according to claim 7, wherein the eluent comprises a mixture of organic solvents or inorganic solvents in different proportions.

9. The method according to claim 8, wherein the organic solvent is selected from the group consisting of acetonitrile, methanol, ethanol, acetic acid, and ethyl acetate, and the inorganic solvent is selected from the group consisting of water, physiological saline, ammonium acetate, and sodium citrate.

10. The method according to claim 7, wherein the sample spot volume is between 0.5 μL and 5.0 μL.

11. The method according to claim 7, wherein the sample spot volume is between 0.5 μL and 1.0 μL.

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