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Optimal labeling conditions of (68)Ga-DOTA-iNGR and its biodistribution in mice

Objective 
To explore the optimal conditions of preparing 68Ga-DOTA-iNGR (NGR peptide containing CendR motif), to evaluate its biodistribution in normal mice and to perform microPET imaging in tumor-bearing nude mice. 
 
 
Methods 
68Ga fresh eluent (200 μl, 92.5-129.5 MBq) obtaining with 68Ge-68Ga radionuclide generator was used to label DOTA-iNGR. The optimal conditions of labeling including pH, temperature, reacting time and concentration of DOTA-iNGR were determined. Then, the in vitro and in vivo stability and octanol/water partition coefficient of 68Ga-DOTA-iNGR were further analyzed. The biodistribution in normal Kunming mice was examined at 10, 20, 40, 60 and 120 min after injection of 68Ga-DOTA-iNGR. Nude mice bearing HT-1080 (CD13-positive) and HT-29 (CD13-negative) tumors were established and underwent microPET imaging at 1 h after the intravenous injection of 68Ga-DOTA-iNGR. Data were analyzed using independent-sample t test. 
 
 
Results 
The optimal conditions of labeling was mixing 2 μg DOTA-iNGR peptide with 200 μl 68Ga (92.5-129.5 MBq) at pH 4.0, temperature 90-100 ℃ for 5-10 min. Under this condition, labeling rate reached (97.5±1.3)%. The radiochemical purity of 68Ga-DOTA-iNGR in both saline (room temperature) and mouse serum (37 ℃) were both above 95% after 4 h incubation, and the radiochemical purity in urine was greater than 85% after 1 h metabolism in vivo. The partition coefficient was -2.71±0.18. In normal mice, majority of 68Ga-DOTA-iNGR was excreted from kidneys with a rapid clearance from blood. The in vivo microPET imaging showed that 68Ga-DOTA-iNGR was remarkably accumulated in the CD13-positive HT-1080 tumor. 
 
 
Conclusions 
Labeling DOTA-iNGR with 68Ga under our condition is a simple and efficient procedure with high labeling rate and high specificity. The product 68Ga-DOTA-iNGR has high stability, ideal biodistribution, and specific binding to CD13-positive tumor, which means that it′s a very promising molecular probe for noninvasively detecting CD13-positive tumor. 
 
 
Key words: 
Asparagine-glycine-arginine; DOTA; Isotope labeling; Gallium radioisotopes; Mice