title: Radiolabelling of peptides for PET, SPECT and therapeutic applications using a fully automated disposable cassette system.
abstract: OBJECTIVE
  Radiolabelled somatostatin analogues have found wide clinical use in nuclear medicine for both diagnostic and therapeutic applications. Here, we describe the development of a fully automated synthesis system allowing radiolabelling of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-derivatized peptides with ⁶⁸Ga/¹¹¹In/¹⁷⁷Lu and ⁹⁰Y, meeting radiation safety and pharmaceutical requirements.
  
  
  METHODS
  The system consists of a syringe pump, a holder for insertion of a single use multivalve cassette, a heater and a removable radiation shielding. ⁶⁸Ga labelling was performed in acetate buffer and ¹⁷⁷Lu, ⁹⁰Y and ¹¹¹In labelling in ascorbate buffer, respectively, followed by purification on a C18 cartridge and final sterile filtration. Cross-contamination was prevented by using disposable cassettes and also by ensuring pharmaceutical standards. Radiochemical purity (RCP) was determined by instant thin-layer chromatography on silica gel impregnated glass fibres and reversed-phase high performance liquid chromatography.
  
  
  RESULTS
  ⁶⁸Ga-DOTA-peptides were prepared with high RCP (>91%) and radiochemical yields (RCY>80% decay corrected) and ⁶⁸Ge content was less than 0.0001% in all cases. Synthesis time did not exceed 30 min. ¹¹¹In, ¹⁷⁷Lu and ⁹⁰Y labelling of DOTA-peptides resulted again in high yields (approximately 90%) and RCP (approximately 95%) and total synthesis time of less than 45 min. Radiation dose to fingers was considerably reduced when compared with manual labelling procedures.
  
  
  CONCLUSIONS
  The described system allows fully automated, aseptic preparation of DOTA-peptides radiolabelled with different radionuclides in high radiochemical yields and pharmaceutical quality suitable for clinical application.
authors.affiliation: Clinical Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria. milospetrik@seznam.cz
authors.forename: Milos
authors.initials: M
authors.lastname: Petrik
authors.forename: Peter A
authors.initials: PA
authors.lastname: Knetsch
authors.forename: Roger
authors.initials: R
authors.lastname: Knopp
authors.forename: Giovanni
authors.initials: G
authors.lastname: Imperato
authors.forename: Meltem
authors.initials: M
authors.lastname: Ocak
authors.forename: Elisabeth
authors.initials: E
authors.lastname: von Guggenberg
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.forename: Roland
authors.initials: R
authors.lastname: Silbernagl
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
mesh_terms: D001331:Automation; D004209:Disposable Equipment; D004869:Equipment Safety; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007553:Isotope Labeling / Q000295:instrumentation*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011874:Radiometry; D012371:Robotics; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid