title: Enhancement of reaction conditions for the radiolabelling of DOTA-peptides with high activities of yttrium-90.
abstract: Peptide receptor radionuclide therapy (PRRT) has recently expanded due to radiolabelling of DOTA-peptides, such as the somatostatin analogues [DOTA(0), Tyr(3)]octreotate (DOTATATE). The achievement of high specific activities during procedures has been indicated as the critical factor to consent effective therapy. Several radiochemical factors may negatively impact reaction procedures such as pH, temperature and time of reaction. Our study was undertaken to explore the influence of radiochemical parameters, such as time of incubation, on reaction kinetics during the radiolabelling of DOTATATE with (90)Y.
  
  
  METHODS
  Forty-five radiolabelling procedures were carried out using small volumes of yttrium-90, typically 60-78 μL. At nearly constant pH and temperature two different settings of radiolabelling procedures were implemented, removing the products from the heating water bath approximately after 30 min (group E, early; n=20) and after 39 min (group L, later; n=25). Quality controls were performed by means of both high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC).
  
  
  RESULTS
  Reaction kinetics for (90)Y were found to a provide suitable percentage of incorporation at pH 4.5 for both groups. Reaction temperature was not different between groups E and L. A significant difference was found between the two groups in radiochemical yield, which was 95.6% ± 0.8 for group E and 98.2% ± 1.1 for group L (p<0.0001). The specific activity of the final product was 46.9 MBq/nmol.
  
  
  CONCLUSIONS
  In order to achieve optimal specific activities, pH, temperature and time of reaction necessitate careful evaluation and setting. A statistically significant difference in labelling yield was found between a set of procedures completed at 39 min as compared to that executed at 30 min, keep the reaction pH and temperature constant.
authors.affiliation: Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy. a.nardelli@libero.it
authors.forename: Anna
authors.initials: A
authors.lastname: Nardelli
authors.forename: Elena
authors.initials: E
authors.lastname: Castaldi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ortosecco
authors.forename: Antonio
authors.initials: A
authors.lastname: Speranza
authors.forename: Giovanni
authors.initials: G
authors.lastname: Storto
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pace
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
mesh_terms: D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D007700:Kinetics; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D015021:Yttrium Radioisotopes / Q000737:chemistry*
chemical_list: C476041:DOTA-Tyr(1)-octreotate; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D015282:Octreotide