dc.contributor.author |
Nadeem, Qaisar |
|
dc.date.accessioned |
2017-12-05T04:45:36Z |
|
dc.date.accessioned |
2020-04-15T03:58:43Z |
|
dc.date.available |
2020-04-15T03:58:43Z |
|
dc.date.issued |
2014 |
|
dc.identifier.uri |
http://142.54.178.187:9060/xmlui/handle/123456789/11683 |
|
dc.description.abstract |
The technetium ( 99m Tc) radiopharmaceuticals have been used for
diagnosis of many diseases especially cancer in nuclear medicine for many
years ago. Currently, 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.
Many chelators have been developed as bifunctional chelators for
99m
conjugation to peptides as well as for chelation with
Tc.
Small size
chelators are desireable for labeling the small peptides. One of the most
important requirements of radiopharmaceuticals is an aqueous phase labeling
the biomolecules to
99m
Tc. These requirements must meet in order to use for
nuclear medicine. In this context, cyclopentadiene (Cp - ) is obviously as a
good choice of chelator due to its small size and low molecular weight. The
99m
Tc radiolabeled peptide comprising Cp - core have not been synthesized in
an aqueous phase. Instead, they have been synthesized by double ligand
transfer approach in an organic solvent using harsh reaction conditions which
are still not suitable for routing use.
In this study we describe the syntheses of half-sandwich complexes of
the type [ 5 -Cp(CONH-R)M(CO) 3 ] with M=Re or
99m
Tc. The R group
represents different tri-peptides which display high binding affinities for
oligopeptide transporters PEPT2 and cyclic RGD peptides which have high
binding affinity with integrin family receptor. The
99m
Tc complexes [( 5 -
CpCONH-R) 99m Tc(CO) 3 ] were prepared directly from [ 99m Tc(OH 2 ) 3 (CO) 3 ] + and
Diels-Alder dimerized, cyclopentadienyl derivatized peptides in an aqueous
phase. 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 [( 5 -Cp) 99m Tc(CO) 3 ] tag. The Diel-Alder products
[(HCpCONH-R) 2 ] containing selected peptides were synthesized from Thiele’s
acid [(HCp-COOH) 2 ] via double peptide coupling. The peptides of different
sequences in this study were prepared through solid phase peptide synthesisxiv
(SPPS). The Re-complexes [( 5 -CpCONH-R)Re(CO) 3 ] were synthesized by
attaching [(Cp-COOH)Re(CO) 3 ] directly to the N-terminus amino group of
peptides as prepared from SPPS. The authenticity of the
99m
Tc-complexes is
confirmed by HPLC retention time comparison with the corresponding
rhenium complexes, fully characterized by spectroscopic techniques. |
en_US |
dc.description.sponsorship |
Higher Education Commission, Pakistan |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
Quaid-e-Azam Campus, Lahore, Pakistan |
en_US |
dc.subject |
Natural Sciences |
en_US |
dc.title |
DEVELOPMENT OF NOVEL RADIOLABELED POLYDENTATE LIGANDS AS POTENTIAL DIAGNOSTIC PROBES |
en_US |
dc.type |
Thesis |
en_US |