Experimental study of labeling and biodistribution of 68Ga-NOTA-Duramycin

Abstract

Objective To synthesize 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-Duramycin （NOTA-Duramycin） and evaluate its biodistribution and kinetics in mice and a myocardial ischemia and reperfusion injury porcine model. Methods NOTA-Duramycin was synthesized by the solid phase method and labeled with 6SGa at room temperature. Radiochemical purity and radiolabeling yield were analyzed by HPLC. Stability in vitro and biodistribntion of 68Ga-NOTA-Duramycin in normal mice were studied. Myocardial ischemia and repeffusion injury in porcine models （n =6） was induced with balloon angioplasty. 68Ga-NOTA-Duramycin （37.0 MBq） was injected intravenously and PET/CT images were acquired at 1 h post injection. Myocardial tis- sues were analyzed to confirm the presence of cell death. Results 68Ga-NOTA-Duramycin was easily prepared at room temperature with high radiolabeling yield （92.5 ± 2.1 ）% and radiochemical purity （ 〉 90% ）, and its stability in vitro was satisfactory. The biodistribution of 68 Ga-NOTA-Duramycin in the blood, heart, liver, spleen, lung and kidney was （23.50±15.38） %ID/g, （8.53 ±4.52） %ID/g, （8.26±2.24） %ID/g, （2.12±O. 28 ） % ID/g, （5.02 ± 1.46） % ID/g, （50.62 ± 54.24） % ID/g at 5 min post-injection and （1.83±0.31） %ID/g, （1.05 ±0.31） %ID/g, （0.97 ±0.28） %ID/g, （0.68 ±0.27） %ID/g, （2. 15 ±0.90） % ID/g, （8.12 ±2.74） %ID/g at 60 rain postinjection, respectively. The compound washed out quickly from the circulation via urine excretion. PET/CT showed increased uptake of 68Ga-NOTA-Duramycin by lesions with ischemia and reperfusion injury in porcine models, which was histologically confirmed. Conclusions 68Ga-NOTA-Duramycin can he easily synthesized at room temperature and can detect ischemia and reperfusion injury in porcine models effectively. It may serve as a potential radiotracer for the detection of apoptosis. Key words: NOTA-Duramycin ; Gallium radioisotopes ; Pharmacokinetics ; Cell apoptosis ; Animals, laberatory ; Mice ; Swine