Synthesis and optimization of the labeling procedure of 99mTc-HYNIC-interleukin-2 for in vivo imaging of activated T lymphocytes.
BACKGROUND
We have previously described the labeling of interleukin-2 (IL2) with (123)I and (99m)Tc-N(3)S. Both radiopharmaceuticals were successfully applied in humans to image several inflammatory lesions and autoimmune diseases characterized by tissue infiltrating lymphocytes expressing the IL2 receptor (CD25). However, both radiopharmaceuticals had some specific disadvantages, such as cost and time of synthesis.


METHODS
Here, we describe a new improved method for labeling interleukin-2 with (99m)Tc using HYNIC-NHS and tricine as coligand. Several optimizations of reagent concentrations and labeling conditions were performed in order to standardize the procedure. After labeling, IL2 was purified by tC2 reverse-phase chromatography and tested in vitro and in vivo, in mice and in a normal volunteer. Results showed that this labeling procedure is cheap, fast, reliable, and reproducible, leading to a product with high specific activity (153 µCi/µg), high stability and capable of binding in vitro to CD25 positive cells. In vivo biodistribution in mice and human volunteer did not show any significant different from (99m)Tc-N(3)S-IL2.


CONCLUSIONS
In conclusion, the optimization of (99m)Tc-HYNIC-IL2 has a great advantage in terms of cost and time of production and a simple kit formulation can be considered for routine application to study patients affected by autoimmune diseases, graft rejection, or other chronic inflammatory disorders.
D'Alessandria
Calogero
C
Nuclear Medicine Unit, 2nd Faculty of Medicine, University Sapienza, Rome, Italy.
di Gialleonardo
Valentina
V
Chianelli
Marco
M
Mather
Stephen J
SJ
de Vries
Erik F J
EF
Scopinaro
Francesco
F
Dierck
Rudi A
RA
Signore
Alberto
A
D000818:Animals; D002853:Chromatography, Liquid; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry*; D008213:Lymphocyte Activation; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000276:immunology*; D014018:Tissue Distribution
D007376:Interleukin-2; D015609:Organotechnetium Compounds; C481016:technetium Tc 99m interleukin 2