INTRODUCTION The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of 125I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3). For radioimmunotherapy, 18.5 MBq 131I-ATPS mAb (n = 7), isotype immunoglobulin G (IgG) (n = 6), and vehicle (n = 6) were injected into MKN-45 tumor-bearing mice for 4 weeks, and tumor volume and percentage of tumor growth inhibition (TGI) were compared each week. RESULTS MKN-45 cells showed the highest in vitro cellular binding after 4 hours (0.00324 ± 0.00013%/μg), which was significantly inhibited by unlabeled ATPS mAb at concentrations of greater than 0.4 μM. The in vitro retention rate of 125I-ATPS mAb in MKN-45 cells was 64.1% ± 1.0% at 60 minutes. The highest tumor uptake of 125I-ATPS mAb in MKN-45 tumor-bearing mice was achieved 24 hours after injection (6.26% ± 0.47% injected dose [ID]/g), whereas tumor to muscle and tumor to blood ratios peaked at 48 hours. The 24-hour tumor uptake decreased to 3.43% ± 0.85% ID/g by blocking with unlabeled ATPS mAb. After 4 weeks of treatment, mice receiving 131I-ATPS mAb had significantly smaller tumors (679.4 ± 232.3 mm3) compared with control (1687.6 ± 420.4 mm3, P = .0431) and IgG-treated mice (2870.2 ± 484.1 mm3, P = .0010). The percentage of TGI of 131I-ATPS mAb was greater than 50% during the entire study period (range: 53.7%-75.9%). CONCLUSION The specific binding and antitumor effects of radioiodinated ATPS mAb were confirmed in in vitro and in vivo models of stomach cancer.

中文翻译：

---

放射性标记的抗腺苷三磷酸合酶单克隆抗体作为靶向血管生成的鼻咽癌剂。

引言评估了放射性碘标记的抗腺苷三磷酸合酶单克隆抗体（ATPS mAb）作为Theragnostic剂同时进行癌症成像和治疗的潜力。方法用放射性碘标记三磷酸腺苷合成酶单克隆抗体，然后在6种不同的癌细胞系中测定放射性示踪剂的摄取。在将125 I-ATPS mAb静脉注射到MKN-45荷瘤小鼠（n = 3）中24和48小时后，评估了体内生物分布。对于放射免疫疗法，将18.5 MBq 131I-ATPS mAb（n = 7），同种型免疫球蛋白G（IgG）（n = 6）和媒介物（n = 6）注入MKN-45荷瘤小鼠4周，然后将肿瘤每周比较肿瘤生长抑制（TGI）的体积和百分比。结果MKN-45细胞在4小时后显示出最高的体外细胞结合率（0。00324±0.00013％/μg），当浓度大于0.4μM时，未标记的ATPS mAb会显着抑制这种情况。在60分钟时，125I-ATPS mAb在MKN-45细胞中的体外保留率为64.1％±1.0％。注射MKN-45的荷瘤小鼠在注射后24小时达到最高的125I-ATPS mAb肿瘤吸收（6.26％±0.47％注射剂量[ID] / g），而肿瘤与肌肉和肿瘤与血液的比率最高达到48小时。通过用未标记的ATPS mAb阻断，24小时肿瘤摄取降低至3.43％±0.85％ID / g。治疗4周后，与对照组（1687.6±420.4 mm3，P = .0431）和接受IgG处理的小鼠（2870.2±484.1 mm3，P =。）相比，接受131I-ATPS mAb的小鼠的肿瘤明显较小（679.4±232.3 mm3）。 0010）。在整个研究期间，131I-ATPS mAb的TGI百分比均大于50％（范围：53.7％-75.9％）。