Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with (131)I or (111)In: an intrapatient comparison.

Abstract

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.

• Authors: Adrienne H Brouwers, Wilhelmina C A M Buijs, Egbert Oosterwijk, Otto C Boerman, Carola Mala, Pieter H M De Mulder, Frans H M Corstens, Peter F A Mulders, Wim J G Oyen
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 10 Pt 2 Pg. 3953S-60S (Sep 01 2003) ISSN: 1078-0432 [Print] United States
• PMID: 14506194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• G250 monoclonal antibody
• Indium Radioisotopes
• Iodine Radioisotopes

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Carcinoma, Renal Cell (diagnosis, therapy)
• Female
• Humans
• Indium Radioisotopes
• Injections, Intravenous
• Iodine Radioisotopes
• Kidney Neoplasms (diagnosis, therapy)
• Male
• Middle Aged
• Neoplasm Metastasis
• Quality Control
• Radioimmunodetection (methods)
• Radioimmunotherapy (methods)
• Time Factors
• Tissue Distribution