title: Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients.
abstract: The integrin alpha v beta3 receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, 18F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET.
  
  
  METHODS
  The biodistribution of 18F-AH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of 18F-AH111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues.
  
  
  RESULTS
  The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the 18F-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. 18F-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor.
  
  
  CONCLUSIONS
  18F-AH111585 designed to bind the alpha v beta3 integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.
authors.affiliation: Department of Oncology, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Kenny
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Inger
authors.initials: I
authors.lastname: Oulie
authors.forename: Kaiyumars B
authors.initials: KB
authors.lastname: Contractor
authors.forename: Matthew
authors.initials: M
authors.lastname: Miller
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Spinks
authors.forename: Brian
authors.initials: B
authors.lastname: McParland
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Cohen
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Hui
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Safiye
authors.initials: S
authors.lastname: Osman
authors.forename: Matthias
authors.initials: M
authors.lastname: Glaser
authors.forename: David
authors.initials: D
authors.lastname: Turton
authors.forename: Adil
authors.initials: A
authors.lastname: Al-Nahhas
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009842:Oligopeptides / Q000378:metabolism*; D009928:Organ Specificity; D010455:Peptides / Q000009:adverse effects / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C530281:AH 111585; D009842:Oligopeptides; D010455:Peptides; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid