Ciprofloxacin complexes with technetium-99M for differential diagnosis of infection

Postgraduate Thesis uoadl:1319944 675 Read counter

Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Ραδιοφαρμακευτική Χημεία
Library of the School of Science
Deposit date:
2016-09-09
Year:
2016
Author:
Παπασάββα Αφροδίτη
Supervisors info:
Τσοτίνης Ανδρέας Καθηγητής (Επιβλέπων), Παπαδόπουλος Μηνάς Ερευνητής Α΄, Πιρμεττής Ιωάννης Ερευνητής Α΄
Original Title:
Σύμπλοκα σιπροφλοξασίνης με 99mTc για διαφορική διάγνωση της λοίμωξης
Languages:
Greek
Translated title:
Ciprofloxacin complexes with technetium-99M for differential diagnosis of infection
Summary:
Differential diagnosis of infection by aseptic inflammation is a major problem
in clinical practice. Infection specific imaging agents, preferably labelled
with 99mTc, will contribute to the discrimination between infectious and
sterile inflammation with nuclear medicine techniques.
Aiming at novel infection imaging agents, we report herein the synthesis,
characterization and preliminary evaluation of 99mTc complexes bearing the
broad spectrum antibiotic ciprofloxacin.
For such purposes, the fac-[99mTc(CS2Cip)(PPh3)(CO)3], 2’ has been synthesized
after reaction of PPh3 with the intermediate fac-[99mTc(CO)3(CS2Cip)(H2O)], 1’,
where the ciprofloxacin derivative CS2Cip acts as a bidentate ligand. However,
accelerated conditions in the same reaction result in the formation of the
mixed ligand complex fac-[99mTc(CS2Cip)(PPh3)2(CO)2], 3’.
In addition to this, the fac-[99mTc(DDC)(IsoCip)(CO)3], 4’ has been
synthesized after reaction of DDC and IsoCip with the precursor
fac-[99mTc(H2O)3(CO)3]+, where the ciprofloxacin derivative IsoCip acts as a
monodentate ligand.
The 99mTc complexes 1’-4’ were prepared in high yield and their identity was
established by comparative HPLC studies using the analogous fully characterized
Re complexes 1-4 as reference. Complexes were found to be stable in the
reaction vial for up to 24 hours as well as in challenge experiments with
histidine and cysteine.
For complex 2’, in biodistribution studies low accumulation in normal tissue
was observed resulting in high infected to normal tissue ratio (6.2). In
addition, the low accumulation in tissue with aseptic inflammation results in
low aseptic to normal tissue ratio (1.5), indicating selectivity for the
infected tissue. Complexes 3’ and 4’ didn’t show any selectivity for the
infected tissue. Examination of the logP data suggests high lipophilicity for
all complexes. The values of logP are in the range of about 0,70 to 2,03.
The new technetium-99m complexes carrying ciprofloxacin were synthesized in
high yield and radiochemical purity. The complexes are stable in solution and
against trans chelation. Preliminary biological data justifies further
evaluation of 2’ as potential infection imaging agent.
Keywords:
Ciprofloxacin, Technetium-99m, Radiopharmaceuticals, Radiolabelled, Infection
Index:
Yes
Number of index pages:
3
Contains images:
Yes
Number of references:
107
Number of pages:
91
File:
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