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Organometallic ^99mTc-Aquaion Labels Peptide to an Unprecedented High Specific Activity

Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen-PSI, Switzerland
Forschungszentrum Rossendorf, Institut für Radiochemie, Dresden, Germany
Eenheid Organische Chemie Vrije Universiteit Brussel, Brussel, Belgium

Correspondence: For correspondence or reprints contact: André Egli, MD, Paul Scherrer Institute, Center for Radiopharmaceutical Science, Villigen-PSI CH-5232, Switzerland.

ABSTRACT

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/µmol (160 Ci/µmol) 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-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 K_^D values of all investigated NT analogs below 1 nmol/L on colon carcinoma HT29 cells. Biodistribution experiments in BALB/c mice showed complete clearance of (N-histidinyl) acetic acid-NT(8–13) from the blood after 24 h and no unwanted accumulation in any tissue. Conclusion: 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.

Key Words: peptides • ^99mTc • neurotensin • histidine

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