TY - JOUR
T1 - Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with 131I or 111In
T2 - An intrapatient comparison
AU - Brouwers, Adrienne H.
AU - Buijs, Wilhelmina C.A.M.
AU - Oosterwijk, Egbert
AU - Boerman, Otto C.
AU - Mala, Carola
AU - De Mulder, Pieter H.M.
AU - Corstens, Frans H.M.
AU - Mulders, Peter F.A.
AU - Oyen, Wim J.G.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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. Experintental 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.
AB - 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. Experintental 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.
UR - http://www.scopus.com/inward/record.url?scp=0141568092&partnerID=8YFLogxK
M3 - Article
C2 - 14506194
AN - SCOPUS:0141568092
SN - 1078-0432
VL - 9
SP - 3953s-3960s
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -