Methods for making ultrasound contrast agents
Provided herein are improved methods for preparing phospholipid formulations including phospholipid UCA formulations.
1. A method of ultrasound contrast imaging a subject comprising
selecting an MPEG5000-DPPE having a calcium concentration of less than 115 parts per million (ppm),
combining the MPEG5000-DPPE with DPPA, DPPC and propylene glycol, to form a phospholipid solution having a calcium concentration of less than 0.7 ppm,
combining the phospholipid solution with an aqueous solution to form a phospholipid suspension,
activating the phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres,
administering the lipid-encapsulated gas microspheres to a subject, and
obtaining an ultrasound image of the subject.
2. The method of claim 1 , wherein DPPA, DPPC and MPEG-5000-DPPE are present in the phospholipid solution in a mole % ratio of 10 to 82 to 8 (10:82:8).
3. The method of claim 1 , wherein DPPA has a calcium concentration of less than 780 ppm, DPPC has a calcium concentration of less than 90 ppm, and propylene glycol has a calcium concentration of less than 0.7 ppm.
4. The method of claim 1 , wherein the perfluorocarbon gas is perfluoropropane gas.
5. A method of ultrasound contrast imaging a subject comprising
selecting an MPEG5000-DPPE having a combined calcium and magnesium concentration of less than 115 parts per million (ppm),
combining the MPEG5000-DPPE with DPPA, DPPC and propylene glycol, to form a phospholipid solution having a combined calcium and magnesium concentration of less than 0.7 ppm,
combining the phospholipid solution with an aqueous solution to form a phospholipid suspension,
activating the phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres,
administering the lipid-encapsulated gas microspheres to a subject, and
obtaining an ultrasound image of the subject.
6. The method of claim 5 , wherein DPPA, DPPC and MPEG-5000-DPPE are present in the phospholipid solution in a mole % ratio of 10 to 82 to 8 (10:82:8).
7. The method of claim 5 , wherein DPPA has a combined calcium and magnesium concentration of less than 780 ppm, DPPC has a combined calcium and magnesium concentration of less than 90 ppm, and propylene glycol has a combined calcium and magnesium concentration of less than 0.7 ppm.
8. The method of claim 5 , wherein the perfluorocarbon gas is perfluoropropane gas.