title: First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for αvβ3 Integrin Receptor Targeting.
abstract: (68)Ga-NODAGA-THERANOST™ is an αvβ3 integrin antagonist and the first radiolabeled peptidomimetic to reach clinical development for targeting integrin receptors. In this first-in-human study, the feasibility of integrin receptor peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging was confirmed in patients with non-small-cell lung cancer and breast cancer.
  
  
  METHODS
  Patients underwent PET/CT imaging with (68)Ga NODAGA-THERANOST. PET images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2-((18)F) fluoro-d-glucose ((18)F-FDG) findings. Images were obtained 60 minutes postinjection of 300-500 MBq of (68)Ga-NODAGA-THERANOST.
  
  
  RESULTS
  (68)Ga-NODAGA-THERANOST revealed high tumor-to-background ratios (SUVmax=4.8) and uptake at neoangiogenesis sites. Reconstructed fused images distinguished cancers with high malignancy potential and enabled enhanced bone metastasis detection. (18)F-FDG-positive lung and lymph node metastases did not show uptake, indicating the absence of neovascularization.
  
  
  CONCLUSIONS
  (68)Ga-NODAGA-THERANOST was found to be safe and effective, exhibiting in this study rapid blood clearance, stability, rapid renal excretion, favorable biodistribution and PK/PD, low irradiation burden (μSv/MBq/μg), and convenient radiolabeling. This radioligand might enable theranostics, that is, a combination of diagnostics followed by the appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical assessment, treatment response evaluation, prediction of pathologic response, neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine strategies. Further clinical trials evaluating (68)Ga-NODAGA-THERANOST are warranted.
authors.affiliation: 1 THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, ENETS Center of Excellence , Bad Berka, Germany .
authors.forename: Richard P
authors.initials: RP
authors.lastname: Baum
authors.forename: Harshad R
authors.initials: HR
authors.lastname: Kulkarni
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller
authors.forename: Stanley
authors.initials: S
authors.lastname: Satz
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Danthi
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000378:metabolism; D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005710:Gallium Radioisotopes / Q000008:administration & dosage*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D057786:Peptidomimetics / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D039302:Integrin alphaVbeta3; D057786:Peptidomimetics
keywords: 68Ga-NODAGA-THERANOST™; positron emission tomography; αvβ3 receptor targeting