Evaluation of human transferrin radiolabeled with N-succinimidyl 4-[fluorine-18](fluoromethyl) benzoate.
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.
Aloj
L
L
Nuclear Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1180, USA.
Lang
L
L
Jagoda
E
E
Neumann
R D
RD
Eckelman
W C
WC
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
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