For Radioimmunotherapy Of ~ (177) Lu-labeled Anti-egfr Monoclonal Antibody La22: (177) Lu-dota-la22 And ~ (177) Lu-dtpa-la22 Comparative Study

Applying monoclonal antibodies (mAb) binding to epidermal growth factor receptor (EGFR) to imaging and therapy of tumor has been proved to be a valid strategy for cancer. The mAb LA22, which binds specifically to EGFR, was prepared and reported by G. H. Sato in 1980's. In order to develop mAb LA22 for the radioimmunotherapy of cancer, ¹⁷⁷Lu-DOTA-LA22 and ¹⁷⁷Lu-CHX-A"-DTPA-LA22 were prepared, and their in vitro and in vivo characteristics were evaluated.DOTA-NHS and CHX-A"-DTPA were used as bifunctional chelators (BFCs) for LA22 labeling with ¹⁷⁷Lu. The radiochemical purity (RCP) of ¹⁷⁷Lu-DOTA-LA22 and ¹⁷⁷Lu-CHX-A"-DTPA-LA22 was more than 98% after PD-10 column, and the two radiotracers showed excellent in vitro stability in saline, EDTA solution and serum with the RCP＞90% during 72 h after labelling. The in vivo metabolic stability in blood, kidney and liver was also tested using radio-HPLC, and no metabolism was detected during 24 h postinjection. The immunoreactivity of DOTA-LA22 and CHX-A"-DTPA-LA22 was assessed by a competitive assay, and showed similarity with mAb LA22, while the IC5o values were 0.2850 nM for LA22, 0.3762 nM for DOTA-LA22, and 0.3416 nM for CHX-A"-DTPA-LA22, respectively. According to Lindmo's method, the radioimmunoreactive fraction of the two radiotracers was determined on A549 human lung cancer cells, with the Values were 67.1% and 67.3%, respectively. The blood clearance pattern of two radiotracers was defined as two-compartment model, with T_1/2α and T_1/2β calculated to be 1.4 h and 36.2 h (¹⁷⁷Lu-DOTA-LA22), 2.2 h and 64.6 h (¹⁷⁷Lu-CHX-A"-DTPA-LA22), respectively. The biodistribution study was performed in BALB/c nude mice bearing the A549 human lung cancer xenografts. The biodistribution data showed that the tumor uptake of ¹⁷⁷Lu-DOTA-LA22 was higher than that of ¹⁷⁷Lu-CHX-A"-DTPA-LA22, while the uptake of two radiotracers in other tissues had no significant difference except for blood.¹⁷⁷Lu-DOTA-LA22 showed excellent in vitro and in vivo stability as well as tumor targeting. It appears to be an ideal candidate for radioimmunotherapy of lung cancer.