TY - JOUR
T1 - Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin αvβ3 expression in man
AU - Beer, Ambros J.
AU - Haubner, Roland
AU - Sarbia, Mario
AU - Goebel, Michael
AU - Luderschmidt, Stephan
AU - Grosu, Anca Ligia
AU - Schnell, Oliver
AU - Niemeyer, Markus
AU - Kessler, Horst
AU - Wester, Hans Jürgen
AU - Weber, Wolfgang A.
AU - Schwaiger, Markus
PY - 2006/7/1
Y1 - 2006/7/1
N2 - Purpose: The integrin αvβ3 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 [ 18F]Galacto-RGD, a highly αvβ3- selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [18F]Galacto-RGD uptake correlates with αvβ3 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 [18F] 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 [18F] Galacto-RGD. Immunohistochemistry was done using the αvβ3-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of αvβ3-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 αvβ3 expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake. Conclusions: Molecular imaging of αvβ3 expression with [18F]Galacto-RGD in humans correlates with αvβ 3 expression as determined by immunohistochemistry. PET with [ 18F] Galacto-RGD might therefore be used as a new marker of angiogenesis and for individualized planning of therapeutic strategies with αvβ3-targeted drugs.
AB - Purpose: The integrin αvβ3 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 [ 18F]Galacto-RGD, a highly αvβ3- selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [18F]Galacto-RGD uptake correlates with αvβ3 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 [18F] 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 [18F] Galacto-RGD. Immunohistochemistry was done using the αvβ3-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of αvβ3-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 αvβ3 expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake. Conclusions: Molecular imaging of αvβ3 expression with [18F]Galacto-RGD in humans correlates with αvβ 3 expression as determined by immunohistochemistry. PET with [ 18F] Galacto-RGD might therefore be used as a new marker of angiogenesis and for individualized planning of therapeutic strategies with αvβ3-targeted drugs.
UR - http://www.scopus.com/inward/record.url?scp=33746032220&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-0266
DO - 10.1158/1078-0432.CCR-06-0266
M3 - Article
C2 - 16818691
AN - SCOPUS:33746032220
SN - 1078-0432
VL - 12
SP - 3942
EP - 3949
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -