Methods and compositions for the rapid synthesis of radiometal-labeled probes

Patent metadata

Field	Value
Publication number	US-9447149-B2
Application number	US-201313787781-A
Country	US
Kind code	B2
Filing date	Mar 6, 2013
Priority date	Mar 6, 2012
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The present application is directed to rapid and efficient synthesis of radiometal-labeled probes, pharmaceutical compositions comprising radiometal-labeled probes, and methods of using the radiometal-labeled probes. Such radiometal-labeled probes can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT), and therapy studies.

First claim

What is claimed is:

1. A compound according to Formula III:

wherein L is bound to any of the nitrogen atoms of the triazole moiety, wherein L comprises a peptide,
the moiety M comprises a moiety selected from the group consisting of one or more polyethylene glycol units and one or more sugars,
the moiety Q comprises a hexaazamacrobicyclic sarcophagine chelator capable of coordinating a radiometal nuclide, and
the benzene rings may be mono-, di-, tri-, or tetra-substituted with R 1 and R 2 groups selected from the group consisting of H, halide, hydroxy, alkyl, aryl, nitro or amine groups.

2. A rapid, efficient, and catalyst-free click chemistry method for generating radiometal-labeled probes for imaging and therapy comprising: reacting an azido composition, N 3 -L of Formula I with a strained alkyne of Formula II in the absence of a catalyst, according to the following reaction:

wherein L is bound to any of the nitrogen atoms of the triazole moiety, wherein L comprises a peptide,
the moiety M comprises a moiety selected from the group consisting of one or more polyethylene glycol units and one or more sugars,
the moiety Q comprises a hexaazamacrobicyclic sarcophagine chelator capable of coordinating a radiometal nuclide, and
the benzene rings may be mono-, di-, tri-, or tetra-substituted with R 1 and R2 groups selected from the group consisting of H, halide, hydroxy, alkyl, aryl, nitro or amine groups.

3. The method according to claim 2 , wherein the chelator Q is chelated to a radiometal nuclide selected from the group consisting of 61 Cu, 62 Cu, 64 Cu, 67 Cu, 68 Ga, 86 Y, and 89 Zr.

4. The method of claim 2 , wherein the peptide is an RGD peptide.

5. The method of claim 4 , wherein Q is 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine.

6. The method of claim 2 , wherein the groups R 1 and R 2 are all hydrogen and the radionuclide is 64 Cu.

7. The method of claim 2 , wherein L is an RGD peptide, M is PEG, Q is 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (“DiAmSar”), the groups R 1 and R 2 are all hydrogen and the radionuclide is 64 Cu.

Assignees

• Univ Southern California

Inventors

• Chen Kai
• Conti Peter Stephen

Classifications

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title