title: Evaluation of a PACAP Peptide Analogue Labeled with (68)Ga Using Two Different Chelating Agents.
abstract: OBJECTIVE
  The authors have conjugated chelating agents (DOTA and NODAGA) with a peptide (pituitary adenylate cyclase-activating peptide [PACAP] analogue) that has a high affinity for VPAC1 receptors expressed on cancer cells. To determine a suitable chelating agent for labeling with (68)Ga, they have compared the labeling kinetics and stability of these peptide conjugates.
  
  
  METHODS
  For labeling, (68)GaCl3 was eluted in 0.1 M HCl from a [(68)Ge-(68)Ga] generator. The influences of peptide concentration, pH, and temperature on the radiolabeling efficiency were studied. The stability was evaluated in saline, human serum, DTPA, transferrin, and metallic ions (FeCl3, CaCl2, and ZnCl2). Cell binding assay was performed using human breast cancer cells (T47D). Tissue biodistribution was studied in normal athymic nude mice.
  
  
  RESULTS
  Optimal radiolabeling (>95.0%) of the DOTA-peptide conjugates required a higher (50°C-90°C) temperature and 10 minutes of incubation at pH 2-5. The NODAGA-peptide conjugate needed incubation only at 25°C for 10 minutes. Both radiocomplexes were stable in saline, serum, as well as against transchelation and transmetallation. Cell binding at 37°C for 15 minutes of incubation with (68)Ga-NODAGA-peptide was 34.0% compared to 24.5% for (68)Ga-DOTA-peptide. Tissue biodistribution at 1 hour postinjection of both (68)Ga-labeled peptide conjugates showed clearance through the kidneys.
  
  
  CONCLUSIONS
  NODAGA-peptide showed more convenient radiolabeling features than that of DOTA-peptide.
authors: 1 Department of Radiology, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Pardeep
authors: P
authors: Kumar
authors: 1 Department of Radiology, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Sushil Kumar
authors: SK
authors: Tripathi
authors: 2 School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China .
authors: Chang-Po
authors: CP
authors: Chen
authors: 1 Department of Radiology, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Neil
authors: N
authors: Mehta
authors: 1 Department of Radiology, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Bishnuhari
authors: B
authors: Paudyal
authors: 3 Department of Biochemistry and Molecular Biology, Thomas Jefferson University , Philadelphia, Pennsylvania.|4 Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Eric
authors: E
authors: Wickstrom
authors: 1 Department of Radiology, Thomas Jefferson University , Philadelphia, Pennsylvania.|4 Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, Pennsylvania.|5 Department of Radiation Oncology, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors: Mathew L
authors: ML
authors: Thakur
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
keywords: breast cancer; chelating agent; peptides; prostate cancer; radiopharmaceuticals