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Targeting of Metastatic Renal Cell Carcinoma with the Chimeric Monoclonal Antibody G250 Labeled with ¹³¹I or ¹¹¹In

An Intrapatient Comparison¹

Departments of Nuclear Medicine [A. H. B., W. C. A. M. B., O. C. B., F. H. M. C., W. J. G. O.], Urology [E. O., P. F. A. M.], and Internal Medicine [P. H. M. D. M.], University Medical Center Nijmegen, NL-6500 HB Nijmegen, the Netherlands, and Wilex AG, D-81675 Munich, Germany [C. M.]

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 ¹³¹I-cG250. Here, we present a study comparing intrapatiently the accumulation of ¹³¹I-cG250 and ¹¹¹In-cG250 in RCC metastases.

Experimental Design: Five patients were i.v. injected with 222 MBq ¹¹¹In-ITC-DTPA-cG250 and 222 MBq ¹³¹I-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 ¹¹¹In-ITC-DTPA-cG250 images revealed more metastatic lesions (n = 47) than ¹³¹I-cG250 (n = 30). Quantitative analysis of the images showed higher activities of ¹¹¹In-ITC-DTPA-cG250 than ¹³¹I-cG250 in 20 of 25 lesions. The mean overall half-life of both antibody preparations in plasma was similar.

Conclusions: ¹¹¹In-ITC-DTPA-cG250 outperformed ¹³¹I-cG250 for visualization of metastatic RCC lesions, not just because of the superior gamma camera characteristics of ¹¹¹In, but more importantly, also because higher tumor:blood ratios were obtained. The higher activities of ¹¹¹In-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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