Experimental radioimmunoguided surgery for peritoneal metastases of gastric cancer using anticarcinoembryonic antigen-specific T84.66 F(ab’)2

Abstract

In gastric cancer, peritoneal dissemination is the most frequent cause of the noncurative resection and recurrence after curative resection. We therefore evaluated the feasibility of radioimmunoguided surgery (RIGS) in the treatment of peritoneal metastases of gastric cancer and the use of anti-CEA-specific T84.66 F(ab')2 as an efficient immune agent. Two human gastric cancer cell lines, MKN45 and RF48, were intraperitoneally xenografted into nude mice, which were later injected with 125I-labeled T84.66 F(ab')2. Peritoneal tumors were localized by RIGS 5 days after antibody injection. The minimum number of cells detected by a gamma probe was assayed by in vitro tumor cell localization. We observed 37 peritoneal metastases: 8 invisible (long diameter, <1 mm), 6 small (1- < 5 mm), and 23 large (> or =5 mm) tumors. The accuracy, sensitivity and specificity of RIGS in detecting peritoneal metastasis were 82% (69/84), 76% (28/37), and 87% (41/47), respectively. RIGS accuracy did not differ with respect to tumor diameter. Mean labeling indices over minimal and maximal normal counts were 6.1+/-1.2 (mean +/- SEM) and 4.7+/-1, respectively. Mean scores of CEA immunostaining and silver grains in tumors were significantly higher than those in the nontumor-bearing peritoneum (P < 0.001). There was a close correlation among radioactivity, immunostaining and microautoradiography (P < 0.001-0.005). We observed six false-positive and nine false-negatives which may have been due to high blood background and negative radioimmune reactivity, respectively. 125I-labeled T84.66 F(ab')2 efficiently targeted peritoneally disseminated gastric cancer cells, suggesting that RIGS using this immune agent may accurately detect occult peritoneal metastases in patients with gastric cancer.