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Nucl Med Biol. 2008 Apr;35(3):343-51. doi: 10.1016/j.nucmedbio.2007.12.008.

Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003.

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Nuclear Medicine Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Box 77, New York, NY 10021, USA.



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.

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