title: 99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide.
abstract: In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide.
  
  
  METHODS
  HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice.
  
  
  RESULTS
  All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for 111In-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whereas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribution profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with 111In-DTPA-octreotide, lower ratios in blood and muscle, but considerably higher tumor-to-kidney ratios.
  
  
  CONCLUSIONS
  TOC can be radiolabeled to high specific activities using HYNIC as a bifunctional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc-EDDA-HYNIC-TOC a promising candidate for an alternative to 111In-DTPA-octreotide for tumor imaging.
authors.affiliation: Nuclear Medicine Research Laboratory, St. Bartholomew's Hospital, West Smithfield, London, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Decristoforo
authors.forename: L
authors.initials: L
authors.lastname: Melendez-Alafort
authors.forename: J K
authors.initials: JK
authors.lastname: Sosabowski
authors.forename: S J
authors.initials: SJ
authors.lastname: Mather
mesh_terms: D000818:Animals; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000032:analysis*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D007205:Indium Radioisotopes; D015609:Organotechnetium Compounds; D017481:Receptors, Somatostatin; C094279:indium-111-octreotide; C410263:technetium Tc 99m hydrazinonicotinyl-Tyr(3)-octreotide; D015282:Octreotide