Nucl Med Mol Imaging.  2009 Aug;43(4):330-336.

Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties

• Jeong JM
• Kim YJ
• Lee YS
• Lee DS
• Chung JK
• Lee MC

Abstract

PURPOSE: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide 68Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions.
MATERIALS AND METHODS
Various concentrations of NOTA.3HCl and DOTA.4HCl were labeled with 1 mL 68GaCl3 (0.18~5.75 mCi in 0.1 M HCl) in various pH. NOTA.3HCl (0.373 mM) was labeled with 68GaCl3 (0.183~0.232 mCi/0.1 M HCl 1.0 mL) in the presense of CuCl2, FeCl2, InCl3, FeCl3, GaCl3, MgCl2 or CaCl2 (0~6.07 mM) at room temperature. The labeling efficiencies of 68Ga-NOTA and 68Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated.
RESULTS
68Ga-NOTA and 68Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 degreesC. NOTA was labeled at room temperature while DOTA required heating for labeling. 68Ga-NOTA labeling efficiency was reduced by CuCl2, FeCl2, InCl2, FeCl3 or GaCl3, however, was not influenced by MgCl2 or CaCl2. The protein binding was low (2.04~3.32%). Log P value of 68Ga-NOTA was -3.07 indicating high hydrophilicity.
CONCLUSION
We found that NOTA is a better bifunctional chelating agent than DOTA for 68Ga labeling. Although, 68Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

Keyword

Ga-68; gallium; protein binding; bifunctional chelating agent; generator; NOTA; DOTA

MeSH Terms

Acetone
Copper
Electrons
Enzyme Multiplied Immunoassay Technique
Gallium
Heating
Heterocyclic Compounds
Hot Temperature
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Ions
Magnesium Chloride
Protein Binding
Protein Stability
Acetone
Copper
Gallium
Heterocyclic Compounds
Ions
Magnesium Chloride