期刊
CLINICAL CANCER RESEARCH
卷 12, 期 13, 页码 3942-3949出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-06-0266
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Purpose: The integrin alpha(v)beta(3) plays a key role in angiogenesis and tumor cell metastasis and is therefore an important target for new therapeutic and diagnostic strategies. We have developed [F-18]Galacto-RGD, a highly alpha(v)beta(3)-selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [F-18]Galacto-RGD uptake correlates with alpha(v)beta(3) expression. Experimental Design: Nineteen patients with solid tumors (musculoskeletal system, n = 10; melanoma, n = 4; head and neck cancer, n = 2; gliobastoma, n = 2; and breast cancer, n = 1) were examined with PET using [F-18] Galacto-RGD before surgical removal of the tumor lesions. Snap-frozen specimens (n = 26) were collected from representative areas with low and intense standardized uptake values (SUV) of [F-18] Galacto-RGD. Immunohistochemistry was done using the alpha(v)beta(3)-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of alpha(v)beta(3)-positive vessels were determined and correlated with SUV and tumor/blood ratios (T/B). Results: Two tumors showed no tracer uptake (mean SUV, 0.5 +/- 0.1). All other tumors showed tracer accumulation with SUVs ranging from 1.2 to 10.0 (mean, 3.8 +/- 2.3; T/B, 3.4 +/- 2.2; tumor/ muscle ratio, 7.7 +/- 5.4). The correlation of SUV and T/B with the intensity of immunohistochemical staining (Spearman's r = 0.92; P < 0.0001) as well as with the microvessel density (Spearman's r = 0.84; P < 0.0001) were significant. Immunohistochemistry confirmed lack of alpha(v)beta(3) expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake. Conclusions: Molecular imaging Of alpha(v)beta(3) expression with [F-18]Galacto-RGD in humans correlates with alpha(v)beta(3) expression as determined by immunohistochemistry. PET with [F-18] Galacto-RGD might therefore be used as a new marker of angiogenesis and for individualized planning of therapeutic strategies with alpha(v)beta(3)-targeted drugs.
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