Claims for Patent: 8,562,946

Summary for Patent: 8,562,946

Title:	Miniaturized .sup.62Zn/.sup.62Cu generator for high concentration clinical delivery of .sup.62Cu kit formulation for the facile preparation of radiolabeled Cu-bis(thiosemicarbazone) compounds
Abstract:	A new system accomplishes easy, interchangeable production of multiple PET radiopharmaceuticals through the use of a simplified eluant-only generator and a kit based synthesis technique employing lyophilized or freeze dried ligand. Thus, by simply switching the lyophilized ligand vial kit, any number of .sup.62Cu-labeled radiopharmaceuticals (.sup.62Cu-ligand) can be interchangeably synthesized with only one .sup.62Zn/.sup.62Cu generator.
Inventor(s):	Lacy; Jeffrey L. (Houston, TX)
Assignee:	Proportional Technologies, Inc. (Houston, TX)
Application Number:	13/234,784
Patent Claims:	1. A method of producing radiopharmaceutical agents for use in positron emission tomography comprising: providing a column having a small volume capacity; filling a portion of said column with anion exchange resin beads having a small volume between 25 and 100 .mu.l; introducing a .sup.62Zn solution into the column to bond the radioactive isotope to the beads; providing a septum closed vial containing lypholized ligand compound; soluablizing the lypholized compound in the vial by introducing a reconstitution agent; providing a pressurized eluant vessel in fluid communication with the column; releasing eluant from the eluant vessel to flow into the column and through the resin beads to a dispensing point; directing the eluant from the column dispensing point into the vial thereby forming a radiolabeled Cu-ligand compound. 2. The method of claim 1 wherein the compound comprises at least one bis(thiosemicarbazone) compound represented by the following formula: ##STR00002## wherein R.sub.1 and R.sub.2 are independently hydrogen or a hydrocarbyl group; R.sub.3 is hydrogen, a hydrocarbyl or an aryl group; and R.sub.4 is hydrogen or a hydrocarbyl group, wherein any hydrocarbyl or aryl group optionally contains a heteroatom from the group of O, N, S, P, and Si in place of a carbon atom or a halogen atom in place of a hydrogen atom, together with a suitable excipient. 3. The method of claim 1 wherein the reconstitution agent is sterile water. 4. The method of claim 1 wherein the reconstitution agent comprises a buffering agent. 5. The method of claim 4 wherein the buffering agent is sodium acetate. 6. The method of claim 1 wherein the step of providing a lyophilized form of the ligand compound comprises freezing the compound; placing the compound under a vacuum; and removing the water from the compound. 7. The method of claim 1 wherein the radiolabeled Cu-ligand compound comprises a .sup.62Cu-ligand. 8. The method of claim 7 wherein the reconstitution agent comprises 1.8M NaCl and 0.2M HCI. 9. The method of claim 7 wherein the reconstitution agent comprises a 2 molar excess of a buffer. 10. The method of claim 9 wherein the buffer is sodium acetate. 11. The method of claim 1 wherein the dispensing outlet point is a needle tip. 12. The method of claim 1 wherein for each production of a radiopharmaceutical 0.1 to 0.3 mL of eluant is released through the column at a flow rate of 100-500 .mu.L/minute. 13. A method for producing a radiopharmaceutical comprising the steps of: releasing 0.1 to 0.3 mL of an eluant from an elution vessel to flow through a column containing resin beads having a .sup.62Zn radioactive isotope to a needle tip; wherein the eluant is released through the column at a flow rate of 100-500 .mu.L/minute; directing said eluant from the outlet point into a septum closed vial containing a water reconstituted lyophilized bis(thiosemicarbazone) compound of the formula ##STR00003## wherein R.sub.1 and R.sub.2 are independently hydrogen or a hydrocarbyl group; R.sub.3 is hydrogen, a hydrocarbyl or an aryl group; and R.sub.4 is hydrogen or a hydrocarbyl group and wherein any hydrocarbyl or aryl group optionally contains a heteroatom from the group of O, N, S, P, and Si in place of a carbon atom or a halogen atom in place of a hydrogen atom, to form an injectable solution. 14. A method for producing a radiopharmaceutical comprising the steps of: releasing an eluant from an elution vessel to flow through a column containing resin beads having a bound radioactive isotope to a dispensing outlet point; directing said eluant from the outlet point into a septum closed vial containing a water reconstituted lyophilized bis(thiosemicarbazone) compound of the formula ##STR00004## wherein R.sub.1 and R.sub.2 are independently hydrogen or a hydrocarbyl group; R.sub.3 is hydrogen, a hydrocarbyl or an aryl group; and R.sub.4 is hydrogen or a hydrocarbyl group and wherein any hydrocarbyl or aryl group optionally contains a heteroatom from the group of O, N, S, P, and Si in place of a carbon atom or a halogen atom in place of a hydrogen atom, to form an injectable solution. 15. The method of claim 14 wherein the dispensing outlet point is a needle tip. 16. The method of claim 14 wherein the bound radioactive isotope is .sup.62Zn. 17. The method of claim 14 wherein the eluant carries .sup.62Cu to the dispensing outlet point. 18. The method of claim 14 wherein for each production of a radiopharmaceutical 0.1 to 0.3 mL of eluant is released through the column at a flow rate of 100-500 .mu.L/minute. 19. The method of claim 13 wherein said resin beads have a small volume between 25 and 100 .mu.l. 20. The method of claim 14 wherein said resin beads have a small volume between 25 and 100 .mu.l.

Details for Patent 8,562,946

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2023-09-08