title: Toward realization of 'mix-and-use' approach in ⁶⁸Ga radiopharmacy: preparation, evaluation and preliminary clinical utilization of ⁶⁸Ga-labeled NODAGA-coupled RGD peptide derivative.
abstract: BACKGROUND
  The present article demonstrates a 'mix-and-use' approach for radiolabeling RGD peptide derivative with (68)Ga, which is easily adaptable in hospital radiopharmacy practice. The radiotracer thus formulated was successfully used for positron emission tomography (PET) imaging of breast cancer in human patients.
  
  
  METHODS
  The conditions for radiolabeling NODAGA-coupled dimeric cyclic RGD peptide derivative [NODAGA-(RGD)2] with (68)Ga were optimized using (68)Ga obtained from a (68)Ge/(68)Ga generator developed in-house with CeO2-PAN composite sorbent as well as from a commercial (68)Ge/(68)Ga generator obtained from ITG, Germany. Preclinical studies were carried out in C57BL/6 mice bearing melanoma tumors. The radiotracer was prepared in a hospital radiopharmacy using (68)Ga obtained from ITG generator and used for monitoring breast cancer patients by positron emission tomography (PET) imaging.
  
  
  RESULTS
  (68)Ga-NODAGA-(RGD)2 could be prepared with high radiolabeling yield (>98%) and specific activity (~50 GBq/μmol) within 10 min at room temperature by mixing (68)Ga with the solution of the peptide conjugate. In vivo biodistribution studies showed significant uptake (5.24±0.39% ID/g) in melanoma tumor at 30 min post-injection, with high tumor-to-background contrast. The integrin αvβ3 specificity of the tracer was corroborated by blocking study. Preliminary clinical studies in locally advanced breast cancer (LABC) patients indicated specifically high tumor uptake (SUVmax 10-15) with good contrast.
  
  
  CONCLUSIONS
  This is one of the very few reports which presents preliminary clinical data on use of (68)Ga-NODAGA-(RGD)2 and the developed 'mix-and-use' holds tremendous prospect in clinical PET imaging using (68)Ga.
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: sudipta@barc.gov.in.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Rubel
authors.initials: R
authors.lastname: Chakravarty
authors.affiliation: Department of Nuclear Medine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Rakhee
authors.initials: R
authors.lastname: Vatsa
authors.affiliation: Department of Nuclear Medine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Bhusari
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
authors.affiliation: Department of Nuclear Medine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Jaya
authors.initials: J
authors.lastname: Shukla
authors.affiliation: Department of Nuclear Medine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: B R
authors.initials: BR
authors.lastname: Mittal
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: adash@barc.gov.in.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
mesh_terms: D000085:Acetates / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid
keywords: (68)Ge/(68)Ga generator; Angiogenesis; PET; RGD peptide; Radiopharmacy; ‘Mix-and-use’ approach