title: Preparation and evaluation of the tumor-specific antigen-derived synthetic mucin 1 peptide: A potential candidate for the targeting of breast carcinoma.
abstract: The goal of this study was to prepare a synthetic peptide derived from breast tumor associated antigen and to evaluate its potential as a breast cancer imaging agent.
  
  
  
  A mucin 1 derived peptide was synthesized by solid-phase peptide synthesis and examined for its radiochemical and metabolic stability. The tumor cell binding affinity of (99m)Tc-MUC1 peptide was investigated on MUC1-positive T47D and MCF7 breast cancer cell lines. In vivo biodistribution was studied in normal Balb/c mice and in vivo tumor targeting and imaging in MCF7 and T47D tumor-bearing nude mice.
  
  
  
  The synthesized MUC1-derived peptide displayed high radiochemical and metabolic stability. In vitro tumor cell-binding on T47D and MCF7 cell lines demonstrated high affinity of (99m)Tc-MUC1 peptide towards human breast cancer cells (binding affinities in nanomolar range). Pharmacokinetic studies performed on Balb/c mice are characterized by an efficient clearance from the blood and excretion predominantly through the urinary system. In vivo tumor uptake in nude mice with MCF7 tumor xenografts was 2.77±0.63% ID/g as early as 1h p.i. whereas in nude mice with T47D human ductal breast epithelial cancer cells, the accumulation in the tumor was found to be 2.65±0.54% ID/g at 1h p.i. Also tumor lesion was detectable in γ-camera imaging. The tumor uptake values were always higher than the blood and muscle uptake, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios. A low to moderate (<5% ID/g) accumulation and retention of (99m)Tc-MUC1 was found in the major organs (i.e., lungs, stomach, liver, intestines, kidneys, etc.) in both normal and tumor-bearing mice.
  
  
  
  This study suggests that (99m)Tc-MUC1 tumor-antigen peptide may be a potential candidate for the targeted imaging of MUC1-positive human tumors and warrants further investigation.
authors.affiliation: Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia. Electronic address: sokarvi@kfshrc.edu.sa.
authors.forename: Subhani M
authors.initials: SM
authors.lastname: Okarvi
authors.affiliation: Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al Jammaz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D003545:Cysteine / Q000737:chemistry; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D021381:Protein Transport; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D018396:Mucin-1; D010446:Peptide Fragments; D013667:Technetium; D003545:Cysteine
keywords: (99m)Tc; Biodistribution; Breast carcinoma; Mucin 1; Small peptide; Tumor-antigens