Program

PO4-7-1

Radio-Labeled Peptides as an Imaging Probes

[Speaker] Muhammad Abdul Qadir:1
[Co-author] Qasir Nadeem:1
1:Institute of Chemistry, University of the Punjab, Lahore, Pakistan

Target specific radiopharmaceuticals containing peptides have become more interesting due to increasing the knowledge of receptor binding affinity of specific peptides, as well as ease of chemical modification of peptide sequences.

 Complexing agents have been developed as bifunctional agents for conjugation to peptides as well as for chelation with 99mTc. Small complexing agents are prefferable for labeling the small peptides. One of the most important requirements of radiopharmaceuticals is an aqueous phase labeling of the biomolecules i.e. peptides to 99mTc. In this regard, cyclopentadiene (Cp-) is obviously as a good choice of chelator due to its small size and low molecular weight. The 99mTc radio-labeled peptide comprising Cp core have not been synthesized in an aqueous phase. Instead, they have been synthesized by double ligand transfer approach in organic solvent using harsh reaction conditions which are still not suitable for routing use.
In the present work syntheses of half-sandwich type complexes of the type [Cp(CONHR)99mTc(CO)3] in an aqueous phase has been reported. The R indicates different tri-peptides which possess high affinities for oligo-peptide transporters PEPT2; the R also represents cyclic RGD peptides which have high binding affinity with integrin family receptor. The desired sequences of number of tripeptides and cyclic RGD peptides were synthesized through solid phase peptide synthesis (SPPS) manually using standard Fmoc-chemistry on 2-chlorotritylchloride resin. We have synthesized the Diels-Alder product [(HCpCONHR)2] from Thiele's acid [(HCp-COOH)2] via double peptide coupling.
 The 99mTc complexes were synthesized using [99mTc(OH2)3(CO)3]+ and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels-Alder reactions for the preparation of not only small molecules but also of peptides for carrying a [(Cp)99mTc(CO)3] tag.
The Re-complexes [(CpCONHR)Re(CO)3] were synthesized by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as prepared from SPPS. The authenticity of the 99mTc-complexes is confirmed by HPLC retention time comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.
Key Words: Imaging probes, Radio-labeled peptides, 99mTc

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