(99m) Tc And (90) Y-labeled Anti-gastric Cancer Monoclonal Antibody 3h11 Study

The incidence of gastric cancer is rather high in China. In previous clinical studies, ¹³¹I-labeled anti-human gastric cancer monoclonal antibody (mAb) 3H11 disclosed tumor lesions that were not visualized by radiography or CT. In order to improve image quality, ^99mTc-labeled mAb 3H11 was prepared and evaluated in vitro and in vivo. In order to develop the radioimmunotherapy of gastric cancer, ⁹⁰Y-DOTA -3H11 was also prepared and evaluated in vitro and in vivo.The mAb 3H11 was labeled with ^99mTc in direct labeling method (Schwarz) and indirect labeling method, using S-hydrazinonicotinamide (HYNIC) as a bifunctional chelating agent (BFCA). The stability of two preparations was tested in saline and serum at 37℃during 48 h. In addition, Diethylenetriamine pentaacetic acid (DTPA) and cysteine challenge assays were performed. The biodistribution andγimaging in nude mice with human-gastric cancer BGC-823 cells xenografts were studied.1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) was used as a BFCA for ⁹⁰Y labeling. The stability of ⁹⁰Y-DOTA-3H11 was tested in saline and serum at 37℃during 48 h. According to Lindmo's method, the immunoreactive fraction of ⁹⁰Y-DOTA-3H11 was determined on BGC 823 gastric cancer cells. The blood clearance and biodistribution were studied in nude mice with human-gastric cancer xenografts.The labeling yield of ^99mTc-3H11 and ^99mTc-HYNIC-3H11 was more than 95% and 90% respectively, and the radiochemistry purity of two preparations was more than 99% after PD-10 column purification. Two preparations showed good stability in saline and serum during the 48 h incubation period. ^99mTc-3Hl 1 showed release of the radiolabel at a 1000-fold or higher molar excess of cysteine, whereas ^99mTc-HYNIC-3H11 was stable under all conditions. At 24 h post-injection, the mean tumor uptake (%ID/g) was 15.8 (^99mTc-3H11) and 31.2 (^99mTc-HYNIC-3H11), and the radioactive ratios of tumor to blood, tumor to muscle and tumor to stomach were 1.8, 19.0, 9.56 (^99mTc-3H11) and 1.9, 21.4, 15.1 (^99mTc-HYNIC-3H11), respectively. Comparing to control ^99mTc-IgG, The clear images of xenografted tumors were obtained at 24 h post-injection for two preparations.The labeling yield of ⁹⁰Y-DOTA-3H11 was more than 95%, and the radiolabeled antibody was stable in saline and serum with the RCP > 90%. The immunoreactive fraction was 72.4%. The pattern of blood clearance was defined as two-compartment model, with T_1/2α and T_1/2β calculated to be 1.43 h and 69.7 h, respectively. The biodistribution results showed that ⁹⁰Y-DOTA-3H11 was well accumulated in tumor, while the %ID/g of tumors was 36.6%±5.7%, and the ratios of T/NT were 1.26 for blood, 12.80 for muscle, 6.13 for bone, 2.34 for kidney, 1.89 for liver and 10.17 for stomach at 24 h postinjection, respectively.^99mTc-HYNIC-3H11 and ⁹⁰Y-DOTA-3H11 showed excellent in vitro and in vivo stability and tumor targeting. They appear to be ideal candidates for radioimmunoimaging and radioimmunotherapy of gastric cancer.