title: Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Nuclear Medicine, Lehrstuhl II für Organische Chemie, Technische Universität München, Germany. beer@roe.med.tum.de
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.forename: Mario
authors.initials: M
authors.lastname: Sarbia
authors.forename: Michael
authors.initials: M
authors.lastname: Goebel
authors.forename: Stephan
authors.initials: S
authors.lastname: Luderschmidt
authors.forename: Anca Ligia
authors.initials: AL
authors.lastname: Grosu
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Markus
authors.initials: M
authors.lastname: Niemeyer
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000032:analysis* / Q000096:biosynthesis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C423503:fluorogalacto-RGD; D005690:Galactose