Immunohistochemical analysis of intratumoral heterogeneity of [131I]cG250 antibody uptake in primary renal cell carcinomas

Abstract

Summary In previous studies, highly heterogeneous uptake of '3'1-labelled chimeric monoclonal antibody G250 (['3'11]cG250) in prmary renal cell carcinomas has been observed (intratumoral differences > factor 100). In this study, we investigated a possible correlation between intratumoral antibody uptake and four immunohistochemicalty determined parameters: G250 antigen expression, blood (Juweid et al. 1995: Press et al. 1995: Kaminski et al. 1996 more modest results hax-e been reported for solid tumours (Wilder et al. 1996. review). Marked heterogeneitx of intratumoral antibody uptake has frequently been obserned and is thought to be an important factor limiting the therapeutic efficacy of radioimmunotherapy. It has been postulated that heterogeneic antibody uptake mi,ght be explained by heterogeneity in expression of the tumour-associated antigen (Wilder et al. 1996) and/or by xascular parameters such as x ascular volume. blood flow-rate or xascular permeabilitx (Blumenthal et al. 1992). Insight into the factors that determine antibody uptake may lead to approaches to achiex e optimal. more homogeneous antibodv uptake.In a phase I protein dose escalation studx-wxith "II-labelled chimeric MAb G250 (cG250) in patients with primary renal cell

111In-Bevacizumab Imaging of Renal Cell Cancer and Evaluation of Neoadjuvant Treatment with the Vascular Endothelial Growth Factor Receptor Inhibitor Sorafenib

“…Other factors, such as tumor vessel characteristics, appear to be more important. In earlier studies, we have shown that high antigen expression is a prerequisite for high antibody uptake but that fulfillment of other conditions is equally pivotal to establishing high antibody uptake (25). The intratumoral heterogeneity, intrapatient differences, and lack of bevacizumab uptake in a benign VEGF-expressing oncocytoma support this notion.…”

Quantitative intratumoural microdistribution and kinetics of 131I-huA33 antibody in patients with colorectal carcinoma

“…Other studies have not found consistent relationships between degree of vascularity and antibody uptake in tumours [3-5,8,9,27]. Given the avascular nature of the necrotic tumour centre, we conclude that huA33 can penetrate long distances from blood vessels before binding to tumour cells.…”

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250

“…Firstly, targeting of the antibody and thus the intensity of both the radioactive and the fluorescent signal is dependent on the degree and extent of CAIX expression. Although CAIX expression in most ccRCCs is homogeneous, G250-uptake is quite heterogeneous due to differences in perfusion, vascular permeability, and interstitial fluid pressure 19,22 . As a result, uptake of the G250-based tracer may vary substantially between lesions.…”

“…An important advantage of the currently used mAb G250 is that it has been studied extensively in clinical trials over the years [14][15][16][17][18][19][20][21] , indicating that clinical translation of this dual-labeled tracer is feasible. In addition, labeling the antibody preparation with 111 In enables high quality pre-operative whole body SPECT imaging, which can be helpful in clinical decision making in these patients 18 .…”