Methods and compositions for positron emission tomography myocardial perfusion imaging

Patent metadata

Field	Value
Publication number	US-9789211-B2
Application number	US-201314401470-A
Country	US
Kind code	B2
Filing date	Mar 15, 2013
Priority date	May 14, 2012
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

This invention provides compounds and compositions useful as imaging tracers for positron emission tomography myocardial perfusion imaging (PET MPI). Compounds in accordance with embodiments of the invention will generally comprise three structural elements: i) a triphenylphosphonium moiety; ii) a chelating element; and iii) a hydrophobic element. The tracer compounds are preferably radiolabeled with 64 Cu or 18 F. Also provided are methods for synthesizing the compounds, methods for derivatizing the compounds, and derivatives thereof.

First claim

What is claimed is:

1. A multi-unit molecule useful as an imaging tracer, comprising:
one or more cationic units;
one or more hexaaza sacophogine cage (sar) multifunctional chelator units; and
one or more hydrophobic units,
wherein said one or more cationic units, one or more sar multifunctional chelator units and one or more hydrophobic units may be linked directly to each other or via a linker arranged in any sequential order in a linear linkage,
wherein said one or more cationic units is selected from the group consisting of TPP, —P + R 1 R 2 R 3 and —N + R 1 R 2 R 3 , wherein R 1 , R 2 , and R 3 are each independently selected from an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted alkyl, an optionally substituted cycloalky, or an optionally substituted heteroaryl, wherein said one or more sar multifunctional chelator units is one selected from the group consisting of BaBaSar, AnAnSar, BaAnSar, BaMalSar, and MalMalSar,
wherein said one or more hydrophobic units is selected from the group consisting of:

2. The multi-unit molecule of claim 1 , wherein said one or more sar multifuncitional chelator units is complexed with 64 Cu, 68 Ga, or an equivalent thereof.

3. The multi-unit molecule of claim 1 , wherein said one or more sar multifunctional chelator units is functionalized with at least one of N3, alkyne, norbornene, tetrazine, cyclooctyne and cyclooctene.

4. A method of imaging a subject's heart, comprising:
administering a composition containing an effective amount of the multi-unit molecule according to claim 2 ; and
taking images of the subject's heart using a suitable imagining device.

5. A method of forming a imaging tracer of claim 1 , useful as a PET tracer for myocardial perfusion imaging, comprising:
linking one or more cationic units and one or more hydrophobic units to one or more hexaaza sacophogine cage (sar) multifunctional chelator units in a linear arrangement to form a multi-unit molecule, wherein said units may be linked to each other directly or via a linker in any sequential order; and
labeling said multi-unit molecule with a suitable radio-active isotope selected from 64 Cu, 68 Ga, or equivalents thereof.

6. An imaging reagent kit, comprising:
a composition containing a multi-unit molecule according to claim 1 , wherein said multi-unit molecule further includes a 64 Cu label; and
an instruction for producing and administering an imaging tracer using said composition.

Assignees

• Conti Peter S
• Liu Shuanglong
• Li Zibo
• Univ Southern California

Inventors

• Conti Peter S
• Liu Shuanglong
• Li Zibo

Classifications

• A61K49/04 Primary

  X-ray contrast preparations · CPC title

• A61B6/503

  for diagnosis of the heart · CPC title

• A61K51/0482

  chelates from cyclic ligands, e.g. DOTA · CPC title

• A61B6/037

  Emission tomography · CPC title

• A61K51/044 Primary

  having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins (rifampin A61K51/0459) · CPC title