Targeting of Metastatic Renal Cell Carcinoma with the Chimeric Monoclonal Antibody G250 Labeled with 131I or 111In
Purpose: There is increasing evidence that the chimeric monoclonal antibody G250 (cG250) can be internalized by G250 antigen-expressing renal cell carcinoma (RCC) cells. Thus, accumulation in tumors of cG250 labeled with residualizing radionuclides might be higher than that of nonresidualizing 131 I...
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Published in | Clinical cancer research Vol. 9; no. 10; p. 3953s |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Association for Cancer Research
01.09.2003
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Online Access | Get full text |
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Summary: | Purpose: There is increasing evidence that the chimeric monoclonal antibody G250 (cG250) can be internalized by G250 antigen-expressing
renal cell carcinoma (RCC) cells. Thus, accumulation in tumors of cG250 labeled with residualizing radionuclides might be
higher than that of nonresidualizing 131 I-cG250. Here, we present a study comparing intrapatiently the accumulation of 131 I-cG250 and 111 In-cG250 in RCC metastases.
Experimental Design: Five patients were i.v. injected with 222 MBq 111 In-ITC-DTPA-cG250 and 222 MBq 131 I-cG250 on days 0 and 4, respectively. Directly and 4 days after the injection of both antibody preparations, whole body gamma
camera images were acquired. The scintigraphic images were analyzed visually and quantitatively. The radioactivity in tissues
was calculated and expressed as percentage injected dose in organs or percentage injected dose/g in metastases. For the latter,
tumor:blood ratios were also calculated. Twenty-five metastases were analyzed completely.
Results: At 4 days postinjection, the 111 In-ITC-DTPA-cG250 images revealed more metastatic lesions ( n = 47) than 131 I-cG250 ( n = 30). Quantitative analysis of the images showed higher activities of 111 In-ITC-DTPA-cG250 than 131 I-cG250 in 20 of 25 lesions. The mean overall half-life of both antibody preparations in plasma was similar.
Conclusions: 111 In-ITC-DTPA-cG250 outperformed 131 I-cG250 for visualization of metastatic RCC lesions, not just because of the superior gamma camera characteristics of 111 In, but more importantly, also because higher tumor:blood ratios were obtained. The higher activities of 111 In-ITC-DTPA-cG250 in metastatic lesions might be caused by internalization and subsequent intracellular retention of the radiolabel,
implying that in future radioimmunotherapy trials with cG250 in RCC patients, the use of a residualizing radionuclide should
be considered. |
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ISSN: | 1078-0432 1557-3265 |