Purpose: The integrin α_vβ₃ 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 α_vβ₃-selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [¹⁸F]Galacto-RGD uptake correlates with α_vβ₃ 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 α_vβ₃-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of α_vβ₃-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 α_vβ₃ expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake.

Conclusions: Molecular imaging of α_vβ₃ expression with [¹⁸F]Galacto-RGD in humans correlates with α_vβ₃ 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 α_vβ₃-targeted drugs.