title: Development of a (68)Ga-peptide tracer for PET GnRH1-imaging.
abstract: OBJECTIVE
  Total synthesis, quality control and preclinical evaluation of [(68)Ga]-DOTA-triptorelin ([(68)Ga]-DOTA-TRP) is reported as a possible PET radiotracer for GnRH receptor imaging.
  
  
  METHODS
  DOTA-TRP was totally synthesized in two steps and after characterization went through radiolabelling optimization studies followed by tracer stability. The biodistribution of the tracer in normal male rats and 4T1 tumour-bearing mice was performed in 120 min after i.v. injection.
  
  
  RESULTS
  The peptide and the conjugates were synthesized with >95 % chemical purity. [(68)Ga]-DOTA-TRP complex was prepared in high radiochemical purity (>99 %, ITLC, HPLC) and specific activity of 1400-2100 MBq/nM at 95 °C using 40-60 μg of the peptide in 5-7 min followed by solid phase purification. The IC50 [nM] DOTA-TRP was comparable to the intact peptide, 0.11 ± 0.01 and 0.22 ± 0.05, respectively. The biodistribution of the tracer demonstrated kidney, stomach, and testes significant uptake, all in accordance with GnRH receptor ligands. Significant tumour uptake was observed in 4T1 tumour-bearing female mice 30-120 min post-injection with tumour:blood and tumour:muscle ratios of 28 and >50 in 60 min, respectively. Kidney is rapidly washed from the tracer. [(68)Ga]-DOTA-TRP can be proposed as a possible tracer for GnRH-R imaging studies.
authors.affiliation: Department of Chemistry, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Zoghi
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran. ajalili@aeoi.org.ir.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Jalilian
authors.affiliation: Department of Chemistry, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Niazi
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Johari-Daha
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Alirezapour
authors.affiliation: Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Ramezanpour
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D004355:Drug Stability; D005260:Female; D005710:Gallium Radioisotopes; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D017329:Triptorelin Pamoate / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D011498:Protein Precursors; C050866:progonadoliberin I; D017329:Triptorelin Pamoate; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D007987:Gonadotropin-Releasing Hormone
keywords: 4T1; 68Ga; GnRH; Peptide synthesis; Triptorelin