Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man.

Beer, AJ; Haubner, R; Sarbia, M; Goebel, M; Luderschmidt, S; Grosu, AL; Schnell, O; Niemeyer, M; Kessler, H; Wester, HJ; Weber, WA; Schwaiger, M

doi:10.1158/1078-0432.CCR-06-0266

journal article

Titel:: Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man.
Dokumenttyp:: Journal Article; Research Support, Non-U.S. Gov't; Article
Autor(en):: Beer, AJ; Haubner, R; Sarbia, M; Goebel, M; Luderschmidt, S; Grosu, AL; Schnell, O; Niemeyer, M; Kessler, H; Wester, HJ; Weber, WA; Schwaiger, M
Abstract:: PURPOSE: The integrin alpha(v)beta3 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 alpha(v)beta3-selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [18F]Galacto-RGD uptake correlates with alpha(v)beta3 expression. EXPERIMENTAL DESIGN: Nineteen patients with solid tumors (musculoskeletal system, n = 10; melanoma, n = 4; head and neck cancer, n = 2; glioblastoma, 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 alpha(v)beta3-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of alpha(v)beta3-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)beta3 expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake. CONCLUSIONS: Molecular imaging of alpha(v)beta3 expression with [18F]Galacto-RGD in humans correlates with alpha(v)beta3 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 alpha(v)beta3-targeted drugs.
Zeitschriftentitel:: Clin Cancer Res
Jahr:: 2006
Band / Volume:: 12
Heft / Issue:: 13
Seitenangaben Beitrag:: 3942-9
Sprache:: eng
Volltext / DOI:: doi:10.1158/1078-0432.CCR-06-0266
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/16818691
Print-ISSN:: 1078-0432
TUM Einrichtung:: Frauenklinik und Poliklinik; Klinik und Poliklinik für Nuklearmedizin; Klinik und Poliklinik für Orthopädie und Sportorthopädie; Klinik und Poliklinik für RadioOnkologie und Strahlentherapie
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