Methods for Cell Labeling and Medical Imaging

Abstract

Methods of ex vivo labeling of a biological material for in vivo imaging, methods of labeling a biological material in vivo, methods for preparing a labeling agent, and methods for in vivo imaging of a subject using a biological material labeled with a labeling agent are disclosed. In one non-limiting example, the biological material is selected from cells and the labeling agent is a 89 Zr-Desferrioxamine-NCS labeling agent.

What is claimed is: 
     
         1 . A method for preparing a labeling agent, the method comprising:
 (a) providing a compound including a chelating moiety and a conjugation moiety; and   (b) mixing the compound with a radionuclide to create the labeling agent before reacting the compound with an additional moiety,   wherein the chelating moiety includes a hydroxamic acid group and the conjugation moiety includes an isothiocyanate group.   
     
     
         2 . The method of  claim 1 , wherein the additional moiety is a lysine residue. 
     
     
         3 . The method of  claim 1 , wherein the additional moiety is at least one of a liposome, DNA aptamer, RNA aptamer, a virus, nanoparticles, microorganisms, antibodies, proteins, peptides, scaffolds, polymers, and nucleic acids. 
     
     
         4 . The method of  claim 1 , wherein the chelating moiety is a desferrioxamine group. 
     
     
         5 . The method of  claim 1 , wherein the conjugation moiety includes a benzyl group. 
     
     
         6 . The method of  claim 1 , wherein the labeling agent is a  89 Zr-isothiocyanato-benzyl-desferrioxamine. 
     
     
         7 . The method of  claim 1 , wherein the additional moiety is a cell. 
     
     
         8 . The method of  claim 1  wherein:
 the additional moiety is a cell selected from microorganisms, blood-derived cells, cancer cells, stem cells, and dendritic cells. 
 
     
     
         9 . The method of  claim 1 , wherein the additional moiety is a stem cell. 
     
     
         10 . The method of  claim 1 , wherein the additional moiety is a cell surface protein. 
     
     
         11 . The method of  claim 1  wherein the additional moiety is a virus. 
     
     
         12 . The method of  claim 1  wherein:
 the radionuclide is selected from the group consisting of  11 C,  13 N,  15 O,  18 F,  34m Cl,  38 K,  45 Ti,  51 Mn,  52 Mn,  52m Mn,  52 Fe,  55 Co,  60 Cu,  61 Cu,  62 Cu,  64 Cu,  66 Ga,  68 Ga,  71 As,  72 As,  74 As,  75 Br,  76 Br,  82 Rb,  86 Y,  89 Zr,  90 Nb,  94m Tc,  99m Tc,  110m In,  111 In,  118 Sb,  120 I,  121 I,  122 I,  123 I and  124 I. 
 
     
     
         13 . The method of  claim 1  wherein:
 the radionuclide is a positron emitter. 
 
     
     
         14 . The method of  claim 13  wherein:
 the positron emitter is  89 Zr. 
 
     
     
         15 . The method of  claim 1  wherein:
 the additional moiety is a cell, and 
 the method further comprises reacting the compound with the cell to create a labeled cell that has stable retention of radioactivity for at least 1 day after reacting the compound with the cell. 
 
     
     
         16 . The method of  claim 15 , wherein the labeled cell has stable retention of radioactivity for at least 4 days. 
     
     
         17 . The method of  claim 15 , wherein the labeled cell has stable retention of radioactivity for at least 7 days. 
     
     
         18 . The method of  claim 1  wherein:
 the additional moiety is a cell, and 
 the method further comprises reacting the compound with the cell to create a labeled cell having no loss in cellular viability after 7 days of culture. 
 
     
     
         19 . The method of  claim 1  wherein:
 the method further comprises reacting the compound with the additional moiety at a pH range of 7.5-9. 
 
     
     
         20 . The method of  claim 1  wherein:
 the method further comprises reacting the compound with the additional moiety in a time period of 10-40 minutes.