title: Preclinical evaluation of a high-affinity 18F-trifluoroborate octreotate derivative for somatostatin receptor imaging.
abstract: Recent studies have highlighted the high sensitivity of PET imaging with (68)Ga-labeled octreotide derivatives for the detection and staging of neuroendocrine tumors. A somatostatin receptor ligand that is easily radiolabeled with (18)F-fluoride could improve the availability of PET imaging of neuroendocrine tumors. We report an alkyltrifluoroborate-octreotate conjugate that is radiolabeled in a 1-step (18)F exchange reaction in high yield and with high specific activity.
  
  
  METHODS
  We conjugated a new alkyltrifluoroborate to octreotate to obtain AMBF3-TATE, which was stored in 50-nmol aliquots for radiolabeling. (18)F labeling was performed by (18)F-(19)F isotope exchange with (18)F-fluoride, and the tracer was purified by C18 cartridge separation. The radiochemical yield was 20%-25%. PET imaging and biodistribution were performed on mice bearing AR42J tumor xenografts.
  
  
  RESULTS
  AMBF3-TATE bound the somatostatin receptor subtype 2 with high affinity (inhibition constant, 0.13 ± 0.03 nM). Starting with 29.6-37 GBq (0.8-1 Ci) of (18)F-fluoride, more than 7.4 GBq (>200 mCi) of (18)F-AMBF3-TATE were obtained in 25 min (n = 5) with greater than 99% radiochemical purity at high specific activity (>111 GBq [3 Ci]/μmol). (18)F-AMBF3-TATE was stable in plasma. PET imaging and biodistribution showed rapid renal excretion with low liver activity. High tumor uptake (10.11% ± 1.67% injected dose/g, n = 5) was detected at 60 min after injection. Bone uptake was negligible. Tumor-to-liver, tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios (at 60 min) were 26.2 ± 0.8, 25.1 ± 1.0, 89.0 ± 3.1, and 21.3 ± 3.6, respectively.
  
  
  CONCLUSIONS
  (18)F-AMBF3-TATE was radiolabeled in high yield and at high specific activity, did not require high-performance liquid chromatography purification, exhibited unexpectedly high binding affinity to somatostatin receptor subtype 2, and showed excellent pharmacokinetic properties in vivo, with high tumor uptake and high contrast ratios.
authors: Chemistry Department, University of British Columbia, Vancouver, British Columbia, Canada; and.
authors: Zhibo
authors: Z
authors: Liu
authors: BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
authors: Maral
authors: M
authors: Pourghiasian
authors: BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
authors: François
authors: F
authors: Bénard
authors: BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
authors: Jinhe
authors: J
authors: Pan
authors: BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
authors: Kuo-Shyan
authors: KS
authors: Lin
authors: Chemistry Department, University of British Columbia, Vancouver, British Columbia, Canada; and dperrin@chem.ubc.ca fbenard@bccrc.ca.
authors: David M
authors: DM
authors: Perrin
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005462:Fluorine Radioisotopes; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D017481:Receptors, Somatostatin / Q000032:analysis*; D014018:Tissue Distribution
chemical_list: C000606315:AMBF3-TATE; D001896:Boron Compounds; D005462:Fluorine Radioisotopes; D017481:Receptors, Somatostatin; D015282:Octreotide
keywords: 1-step 18F-labeling; 18F-BF3; octreotate; octreotide; positron emission tomography; somatostatin receptor