Smith-Jones Peter M, Pandit-Taskar Neeta, Cao Wei, O'Donoghue Joseph, Philips Martin D, Carrasquillo Jorge, Konner Jason A, Old Lloyd J, Larson Steven M
Nuclear Medicine Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Box 77, New York, NY 10021, USA.
Nucl Med Biol. 2008 Apr;35(3):343-51. doi: 10.1016/j.nucmedbio.2007.12.008.
The in vitro and in vivo behavior of the radiolabeled monoclonal antibody MORAb-003 was investigated as a prelude to a clinical trial.
The cellular retention of 111In- and 131I-labeled MORAb-003 was investigated using IGROV1 and SW620 cells. Biodistribution studies in tumor-bearing mice were performed with the more favorable agent.
Five 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA) molecules were conjugated to MORAb-003 with no apparent loss of immunoreactivity. Radiolabeled MORAb-003 had a high affinity for the folate receptor alpha (FRA) expressed by both IGROV1 and SW620 cells and was found to bind to around 8 x 10(5) and 7 x 10(5) sites/cell, respectively. Both cancer cell lines were found to internalize both 131I- and 111In-labeled MORAb-003, but 111In was retained and 131I was released as iodide. In athymic mice, 111In-DOTA-MORAb-003 was cleared from the blood with a single exponential biological clearance rate of 110 h. The uptake in SW620 tumors was 32+/-5%ID/g after 4 days. The clearance rate of activity from normal organs such as liver, kidney and spleen was similar to the blood clearance and was 5.36%ID/g, 4.03%ID/g and 4.36%ID/g at 1 day postinjection and 2.14%ID/g, 1.65%ID/g and 3.74%ID/g after 8 days, respectively. In a pilot clinical study, the biodistribution and tumor targeting of 111In-MORAb-003 was assessed in three patients undergoing treatment with cold MORAb-003.
MORAb-003 is an attractive antibody for radioimmunoscintigraphy and possibly radioimmunotherapy of FRA-expressing cancers in addition to its potential direct therapeutic effects.
作为一项临床试验的前奏，对放射性标记的单克隆抗体MORAb-003的体外和体内行为进行了研究。
使用IGROV1和SW620细胞研究了111In和131I标记的MORAb-003的细胞内滞留情况。用更具优势的制剂在荷瘤小鼠中进行了生物分布研究。
五个1,4,7,10-四氮杂环十二烷-N,N',N",N'"-四乙酸（DOTA）分子与MORAb-003偶联，免疫反应性无明显丧失。放射性标记的MORAb-003对IGROV1和SW620细胞表达的叶酸受体α（FRA）具有高亲和力，分别发现其与约8×10⁵和7×10⁵个位点/细胞结合。两种癌细胞系均发现可内化131I和111In标记的MORAb-003，但111In被保留，131I以碘化物形式释放。在无胸腺小鼠中，111In-DOTA-MORAb-003以110小时的单指数生物清除率从血液中清除。4天后SW620肿瘤的摄取量为32±5%ID/g。肝脏、肾脏和脾脏等正常器官的活性清除率与血液清除率相似，注射后1天分别为5.36%ID/g、4.03%ID/g和4.36%ID/g，8天后分别为2.14%ID/g、1.65%ID/g和3.74%ID/g。在一项初步临床研究中，对三名接受冷MORAb-003治疗的患者评估了111In-MORAb-003的生物分布和肿瘤靶向性。
MORAb-003是一种有吸引力的抗体，除了其潜在的直接治疗作用外，还可用于放射性免疫闪烁显像以及可能用于对表达FRA的癌症进行放射性免疫治疗。
