title: Evaluation of human transferrin radiolabeled with N-succinimidyl 4-[fluorine-18](fluoromethyl) benzoate.
abstract: Iron metabolism plays a key role in cell proliferation and survival in rapidly growing cancer cells. Uptake is mediated by the carrier protein transferrin. The increased need for iron has been used as a method to target tumors and there is well-documented evidence that certain tumors can be imaged with tracers such as 67Ga, that mimic transferrin-mediated iron uptake. To obtain a tracer that would be better able to quantitate transferrin kinetics and indirectly evaluate iron metabolism, we have labeled human transferrin with the positron emitter, 18F, with a one-step high-specific activity method developed in our laboratory.
  
  
  METHODS
  We measured the binding affinities of [18F]diferric (holo-) and iron-free (apo-) transferrin on two human cell lines. We also compared cellular uptake of [18F]holo-transferrin and [67Ga]citrate in various conditions, and washout of label incorporated into cells.
  
  
  RESULTS
  The binding affinity of [18F]holo-transferrin was found to be the same as that reported for [125I]holo-transferrin. In our hands there was no significant difference in binding affinity between diferric holo-transferrin and iron-free apo-transferrin. [18F]holo-transferrin uptake rapidly reaches a steady-state equilibrium between the intracellular and extracellular environment, while gallium accumulation linearly increases with time. [18F]holo-transferrin is rapidly recycled out of the cell with similar kinetics to those reported for [125I]holo-transferrin.
  
  
  CONCLUSIONS
  [18F]holo-transferrin displays the properties of native transferrin and appears suitable for quantitative evaluation of transferrin kinetics in vivo.
authors.affiliation: Nuclear Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1180, USA.
authors.forename: L
authors.initials: L
authors.lastname: Aloj
authors.forename: L
authors.initials: L
authors.lastname: Lang
authors.forename: E
authors.initials: E
authors.lastname: Jagoda
authors.forename: R D
authors.initials: RD
authors.lastname: Neumann
authors.forename: W C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D001565:Benzoates; D002951:Citrates; D019343:Citric Acid; D005069:Evaluation Studies as Topic; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D013388:Succinimides; D014055:Tomography, Emission-Computed; D014168:Transferrin / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000000981:diagnostic imaging
chemical_list: D001565:Benzoates; D002951:Citrates; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D007457:Iodine Radioisotopes; C092711:N-succinimidyl 4-(fluoromethyl)benzoate; D013388:Succinimides; D014168:Transferrin; D019343:Citric Acid