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Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging

Authors :
Afroditi Papasavva
Nektarios N. Pirmettis
Antonio Shegani
Eleni Papadopoulou
Christos Kiritsis
Maria Georgoutsou-Spyridonos
Dimitrios C. Mastellos
Aristeidis Chiotellis
Patricia Kyprianidou
Maria Pelecanou
Minas Papadopoulos
Ioannis Pirmettis
Source :
Pharmaceutics, Vol 16, Iss 9, p 1210 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97–98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6–2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2′) showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3′) demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Details

Language :
English
ISSN :
19994923
Volume :
16
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.1174247a4d34850822cf8c3390aec40
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics16091210