Claims for Patent: 10,588,988

Summary for Patent: 10,588,988

Title:	Methods and devices for preparation of ultrasound contrast agents
Abstract:	Provided herein are methods and devices for identifying and/or distinguishing UCA formulations and specifically activating such formulations to produce UCA suitable for in vivo use.
Inventor(s):	Robinson; Simon P. (Stow, MA), Walker; Carol (Billerica, MA), Onthank; David C. (Groton, MA), Lazewatsky; Joel (Auburndale, MA), Nguyen; Nhung Tuyet (Westford, MA)
Assignee:	Lantheus Medical Imaging, Inc. (North Billerica, MA)
Application Number:	16/559,528
Patent Claims:	1. A method of using lipid-encapsulated gas microspheres for ultrasound imaging comprising: placing a vial comprising an ultrasound contrast agent (UCA) lipid formulation in a shaking device comprising a holder, a detector and a processor; determining identity of the UCA lipid formulation as either a non-aqueous UCA lipid formulation or an aqueous UCA lipid formulation based on an indicator on the vial that is read by the detector; selecting a shaking rate and duration from pre-set options for non-aqueous and aqueous formulations using the processor; activating the identified UCA lipid formulation to form lipid-encapsulated gas microspheres, by imparting a shaking pattern at the selected shaking rate and for the selected duration, using the shaking device; administering the lipid-encapsulated gas microspheres to a subject; and obtaining an ultrasound image of the subject; wherein the aqueous UCA lipid formulation comprises DPPA, DPPC and MPEG5000-DPPE in an aqueous solvent, and a gas, wherein the non-aqueous UCA lipid formulation comprises DPPA, DPPC and MPEG5000-DPPE in a non-aqueous solvent comprising propylene glycol and glycerol, and a gas, and having less than 5% water (w/w), wherein the detector is an RFID reader, a barcode scanner, a color scanner, or a microchip reader, and wherein the pre-set options comprise a shaking duration of at least 30 seconds. 2. The method of claim 1, wherein one pre-set option comprises a shaking duration of about 45 seconds and a shaking rate of at least 4000 shaking motions per minute. 3. The method of claim 1, wherein the shaking device comprises two or more holders. 4. The method of claim 1, wherein the lipid-encapsulated gas microspheres have a mean diameter of about 1-2 microns. 5. The method of claim 1, wherein the shaking device comprises a battery. 6. The method of claim 1, wherein the holder can accommodate a 35 mm tall and 14.5 mm diameter vial. 7. The method of claim 1, wherein one pre-set option comprises a shaking rate that is at least 4500 shaking motions per minute. 8. The method of claim 1, wherein one pre-set option comprises a period of time that is 45 seconds and a shaking rate that is 4530 shaking motions per minute. 9. The method of claim 8, wherein another pre-set option comprises a period of time that is 45 seconds and a shaking rate that is about 4900 shaking motions per minute. 10. The method of claim 1, wherein the shaking device further comprises at least one storage device configured to store a look-up table that stores the pre-set options. 11. The method of claim 1, wherein the indicator provides a method of use for the identified UCA lipid formulation. 12. A method of using lipid-encapsulated gas microspheres for ultrasound imaging comprising: placing a vial comprising an ultrasound contrast agent (UCA) lipid formulation and associated indicator in a shaking device, wherein the device comprises a holder, a detector, one or more controllers and a processor, reading the indicator on the vial using the detector, and identifying the vial as comprising a non-aqueous or an aqueous UCA lipid formulation based on the indicator and optionally lookup table stored in the device, selecting a set of activation parameters for the identified UCA lipid formulation from a first set of activation parameters for a non-aqueous UCA lipid formulation and a second set of activation parameters for an aqueous UCA lipid formulation, as programmed in the device, using the processor, activating the identified UCA lipid formulation to form lipid-encapsulated gas microspheres, using the selected set of activation parameters specific to the identified UCA lipid formulation using the one or more controllers, wherein activating comprises imparting a shaking pattern on the vial, administering the lipid-encapsulated gas microspheres to a subject, and obtaining an ultrasound image of the subject, wherein the aqueous UCA lipid formulation comprises DPPA, DPPC and MPEG5000-DPPE in an aqueous solvent, and a gas, wherein the non-aqueous UCA lipid formulation comprises DPPA, DPPC and MPEG5000-DPPE in a non-aqueous solvent comprising propylene glycol and glycerol, and a gas, and having less than 5% water (w/w), wherein the detector is an RFID detector, a barcode scanner, a color scanner, or a microchip reader, and wherein the first and the second set of activation parameters comprise a shaking time of at least 30 seconds. 13. A method of using lipid-encapsulated gas microspheres for ultrasound imaging comprising: placing a vial comprising an ultrasound contrast agent (UCA) lipid formulation and associated indicator in a shaking device, wherein the device comprises a holder, a detector and a processor, reading the indicator using the detector, and thereby distinguishing a non-aqueous UCA lipid formulation requiring activation for a first pre-determined period of time that is at least about 30 seconds and/or at a first pre-determined shaking rate that is at least 3000 shaking motions per minute from an aqueous UCA lipid formulation requiring activation for a different pre-determined period of time and/or a different pre-determined shaking rate; activating the non-aqueous UCA lipid formulation, by imparting a shaking pattern using the shaking device, for the first pre-determined period of time and/or at the first pre-determined shaking rate to form lipid-encapsulated gas microspheres; administering the lipid-encapsulated gas microspheres to a subject; and obtaining an ultrasound image of the subject; wherein the detector is an RFID detector, a barcode scanner, a color scanner, or a microchip reader, and wherein the non-aqueous UCA lipid formulation comprises less than 5% water (w/w). 14. The method of claim 13, wherein the non-aqueous UCA lipid formulation comprises DPPA, DPPC and MPEG5000-DPPE. 15. The method of claim 13, wherein the first pre-determined period of time is about 75 seconds. 16. The method of claim 15, wherein the first pre-determined shaking rate is about 4530 shaking motions per minute. 17. The method of claim 13, wherein the first pre-determined shaking rate is at least 4500 shaking motions per minute. 18. The method of claim 13, wherein the first pre-determined shaking rate is about 4900 shaking motions per minute. 19. The method of claim 13, wherein, upon distinguishing the non-aqueous UCA lipid formulation from the aqueous UCA lipid formulation, the shaking device automatically selects the first pre-determined period of time from at least two pre-determined periods of time. 20. The method of claim 13, wherein, upon distinguishing the non-aqueous UCA lipid formulation from the aqueous UCA lipid formulation, the shaking device automatically selects the first pre-determined shaking rate from at least two pre-determined shaking rates. 21. The method of claim 13, wherein the shaking device comprises two or more holders. 22. The method of claim 13, wherein the lipid-encapsulated gas microspheres have a mean diameter of about 1-2 microns. 23. The method of claim 13, wherein the shaking device comprises a battery. 24. The method of claim 13, wherein the holder can accommodate a 35 mm tall and 14.5 mm diameter vial. 25. The method of claim 13, wherein the non-aqueous UCA lipid formulation is activated for 45 seconds at about 4900 shaking motions per minute. 26. The method of claim 13, wherein the first pre-determined shaking rate is at least 5000 shaking motions per minute. 27. A method of using lipid-encapsulated gas microspheres for ultrasound imaging comprising: placing a vial comprising an ultrasound contrast agent (UCA) lipid formulation in a shaking device comprising a holder, a detector, and a processor, determining identity of the UCA lipid formulation as a non-aqueous UCA lipid formulation based at least in part on an indicator on the vial that is read by the detector, selecting a shaking rate and duration from pre-set options for a non-aqueous formulation using the processor, activating the identified UCA lipid formulation to form lipid-encapsulated gas microspheres, by imparting a shaking pattern at the selected shaking rate and for the selected duration, using the shaking device, administering the lipid-encapsulated gas microspheres to a subject; and obtaining an ultrasound image of the subject; wherein the detector is an RFID detector, a barcode scanner, a color scanner, or a microchip reader, and wherein the non-aqueous UCA lipid formulation comprises less than 5% water (w/w). 28. The method of claim 27, wherein the indicator provides a method of use for the identified UCA lipid formulation.