title: Technetium-99m-white blood cell-specific imaging agent developed from platelet factor 4 to detect infection.
abstract: We have developed a leukocyte-avid, 99mTc-labeled peptide (P483H) as a potential imaging agent for infection. P483H contains the heparin-binding region of platelet factor-4 (PF-4) and a lysine-rich sequence for rapid renal clearance. Technetium-99m-P483H was evaluated for its ability to selectively label white blood cells (WBCs) in vitro and to detect focal E. coli infections in rabbits.
  
  
  METHODS
  Technetium-99m-P483H was incubated with citrated whole human blood, layered onto WBC isolation media and subjected to density gradient centrifugation to measure WBC-associated radioactivity. Indium-111-WBCs and 99mTc-gluceptate were used as controls. In the in vivo model, E. coli infected rabbits were imaged and necropsied 4 hr after administration of 99mTc-P483H. Infected and contralateral control muscles were evaluated for %ID, %ID/g, Imax (muscle sample showing the highest uptake, i.e., %ID/g) and Imax-to-blood and Imax-to-control muscle ratios. Indium-111-WBCs, 111In-DTPA, 131I-albumin (HSA), 99mTc-nanocolloid, 67Ga and 99mTc-gluceptate were evaluated as in vivo controls.
  
  
  RESULTS
  Technetium-99m-P483H associated predominantly with WBCs in vitro, and 99m-Tc-P483H provided high contrast images of infection in vivo. In vitro, 73% of 99mTc-P483H radioactivity was associated with WBCs. Technetium-99m-P483H outperformed 111In-WBCs, 111In-DTPA, 131I-albumin, 99mTc-nanocolloid, 67Ga-citrate and 99mTc-gluceptate with an infection Imax average of 0.062 %ID/g (+/- 0.029; n = 48). Technetium-99m-P483H also outperformed all controls, including 111In-WBCs, 111In-DTPA, 131I-albumin, 99mTc-nanocolloid, 67Ga-citrate and 99mTc-gluceptate. The Imax-to-blood and Imax-to-control muscle ratios for 99mTc-P483H averaged 3.1 (+/- 2.4) and 26.8 (+/- 16.8), respectively, and again outperformed all controls.
  
  
  CONCLUSIONS
  Technetium-99m-P483H associates predominantly with WBCs in vitro and identified focal infections in vivo within 4 hr versus conventional imaging agents. Additionally, the agent showed rapid blood clearance and exclusive renal excretion, which provides a clear abdominal field for imaging abdominal infections.
authors.affiliation: Diatide, Inc., Londonderry, New Hampshire 03053, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Moyer
authors.forename: S
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: J
authors.initials: J
authors.lastname: Lister-James
authors.forename: L R
authors.initials: LR
authors.lastname: Bush
authors.forename: J E
authors.initials: JE
authors.lastname: Cyr
authors.forename: D A
authors.initials: DA
authors.lastname: Snow
authors.forename: D
authors.initials: D
authors.lastname: Bastidas
authors.forename: H
authors.initials: H
authors.lastname: Lipszyc
authors.forename: R T
authors.initials: RT
authors.lastname: Dean
mesh_terms: D000818:Animals; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D005490:Focal Infection / Q000000981:diagnostic imaging*; D005710:Gallium Radioisotopes; D006801:Humans; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D007962:Leukocytes; D015609:Organotechnetium Compounds; D010455:Peptides; D010978:Platelet Factor 4; D011506:Proteins; D011817:Rabbits; D011877:Radionuclide Imaging; D013400:Sugar Acids; D013667:Technetium; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D010455:Peptides; D011506:Proteins; D013400:Sugar Acids; C100521:technetium Tc 99m P483H; D010978:Platelet Factor 4; D013667:Technetium; C100014:technetium Tc 99m gluceptate