To explore the optimal labeling conditions of ¹⁷⁷Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-D-Phe1-Tyr3-Thr8-octreotide (TATE), and evaluate its biodistribution and imaging characteristics in mice.

The reaction temperature, pH, reaction time and other labeling conditions were changed to realize the rapid labeling of NOTATATE by ¹⁷⁷Lu. The optimal labeling conditions, radiochemical purity, in vitro stability, plasma protein binding rate, and lipid-water partition coefficient were determined. Twenty-four normal KM mice were divided into 6 groups by random number table method. After injected with 3.7 MBq ¹⁷⁷Lu-NOTATATE through tail vein, they were sacrificed at 0.5, 1, 4, 24 h and 4, 6 d respectively to research the biological distribution (injection dose rate per gram of tissue percentage, %ID/g). Six normal mice were randomly divided into 2 groups and injected with 11.1 MBq ¹⁷⁷Lu-NOTATATE and ¹⁷⁷Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)TATE, respectively. SPECT planar imaging was performed at 1, 2, 3 h after injection. Another 8 mice were divided into 4 groups, injected with 3.7, 7.4, 18.5 MBq ¹⁷⁷Lu-NOTATATE and saline respectively for an acute toxicity test.

At pH 5 and reaction temperature between 95 ℃ and 100 ℃ for 15 min, the labeling rate could reach more than 98%. After being placed in human serum for 24 h, the radiochemical purity was still higher than 95%. The plasma protein binding rate of ¹⁷⁷Lu-NOTATATE was (58.6±1.9)% and the lipid-water partition coefficient was 0.048±0.014. In normal mice, the concentration of radioactivity is mainly in the liver, kidney and spleen, especially in the kidney (up to (29.120±1.204) %ID/g after 0.5 h of injection), which is less distributed in the blood and excreted rapidly. Compared with ¹⁷⁷Lu-DOTATATE, ¹⁷⁷Lu-NOTATATE was excreted faster by the kidney. The toxicity study results revealed that no damage was observed in mice of each group, and no obvious damage or inflammatory changes were observed in organ tissue sections.

The optimal labeling condition of ¹⁷⁷Lu-NOTATATE were determined in this study. The physical, chemical, and biological properties of ¹⁷⁷Lu-NOTATATE were proved to be good and safe, and it was excreted faster by the kidney than ¹⁷⁷Lu-DOTATATE. The results of this study lay a foundation for further clinical transformation research.

Receptors, somatostatin; Isotope labeling; Lutetium; Radionuclide imaging; Mice