Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity.
A new peptide labeling method that uses the organometallic aquaion [99mTc(H2O)3(CO)3]+ has been developed.


METHODS
A selection of amino acids was labeled at different concentrations with the organometallic aquaion, and the labeling yield was determined by high-performance liquid chromatography. This investigation has shown histidine to be a very potent ligand, with specific activities of up to 6 TBq/micromol (160 Ci/micromol) ligand. Histidine derivatives have been coupled to neurotensin(8-13) (NT[8-13]) and have been labeled with the aquaion, resulting in high specific activities with (N(alpha)-histidinyl)acetic acid-NT(8-13) similar to those with histidine.


RESULTS
Histidine derivatives of NT(8-13) labeled using this approach fully retained their receptor affinity, showing KD values of all investigated NT analogs below 1 nmol/L on colon carcinoma HT29 cells. Biodistrbution experiments in BALB/c mice showed complete clearance of (N(alpha)-histidinyl)acetic acid-NT(8-13) from the blood after 24 h and no unwanted accumulation in any tissue.


CONCLUSIONS
The novel labeling method using the organometallic 99mTc-aquaion combines the advantage of highest specific activities with minimal functionalization of proteins and peptides under retention of biologic affinity.
Egli
A
A
Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen-PSI, Switzerland.
Alberto
R
R
Tannahill
L
L
Schibli
R
R
Abram
U
U
Schaffland
A
A
Waibel
R
R
Tourwé
D
D
Jeannin
L
L
Iterbeke
K
K
Schubiger
P A
PA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006639:Histidine; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009496:Neurotensin; D010455:Peptides; D019275:Radiopharmaceuticals; D013667:Technetium; D014018:Tissue Distribution
D010455:Peptides; D019275:Radiopharmaceuticals; D009496:Neurotensin; D006639:Histidine; D013667:Technetium