Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties.
- Author:
Jae Min JEONG
1
;
Young Ju KIM
;
Yun Sang LEE
;
Dong Soo LEE
;
June Key CHUNG
;
Myung Chul LEE
Author Information
1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea. jmjng@snu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Ga-68;
gallium;
protein binding;
bifunctional chelating agent;
generator;
NOTA;
DOTA
- MeSH:
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
- From:Nuclear Medicine and Molecular Imaging
2009;43(4):330-336
- CountryRepublic of Korea
- Language:Korean
-
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.
