title: Peptide-based imaging agents targeting phosphatidylserine for the detection of apoptosis.
abstract: A 14-residue phosphatidylserine (PS)-binding peptide FNFRLKAGQKIRFG (PSBP-0) was scanned with Ala. In addition, a radiometal chelator (SAAC) was introduced at selected sites of the lead peptides. Substitution of the Gln(6) residue in PSBP-0 with Ala resulted in a significant increase in binding affinity to PS as determined by surface plasmon resonance sensorgrams. The binding affinity of the resulting peptide FNFRLKAGAKIRFG (PSBP-6, molecular mass = 1623 Da) to PS (K(d) ∼ 100 nM) increased 10-fold as compared to PSBP-0 (K(d) ∼ 1.38 μM). Introduction of SAAC-Re to the N terminus of PSBP-6 further increased the binding affinity of the resulting peptide SAAC(Re)-PSBP-6 (K(d) ∼ 26 nM). SAAC(Re)-PSBP-6 shows specific binding to apoptotic cells in cell-based assays. Biodistribution studies showed significantly higher uptake of SAAC((99 m)Tc)-PSBP-6 in B16/F10 melanoma treated with poly(L-glutamic acid)-paclitaxel than untreated tumors (4.06 ± 0.55% ID/g vs 1.61 ± 0.33% ID/g, P = 0.00011). SAAC((99 m)Tc)-PSBP-6 is a promising probe for noninvasive imaging of apoptotic cells.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, United States.
authors.forename: Chiyi
authors.initials: C
authors.lastname: Xiong
authors.forename: Kari
authors.initials: K
authors.lastname: Brewer
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wen
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010718:Phosphatidylserines / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry; D011868:Radioisotopes; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012211:Rhenium; D013667:Technetium; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D009842:Oligopeptides; D010718:Phosphatidylserines; D011725:Pyridines; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium; D008239:Lysine