Evaluation of 99mTc(I)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Evaluation of 99mTc(I)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection
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| Creator |
Nayak, Dipak Kumar
Baishya, Rinku Halder, Kamal Krishna Sen, Tuhinadri Sarkar, Bharat R. Ganguly, Shantanu Das, M. K Chatterjee Debnath, Mita |
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| Subject |
Infectious Diseases and Immunology
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| Description |
The aim of this study was to develop 99mTc(CO)3-labeled fluoroquinolones as novel SPECT
radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX),
levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a
fac-[99mTc(CO)3(H2O)3]+ precursor. The radiochemical purity of the radiopharmaceuticals
exceeded 97% as determined by thin layer chromatography and HPLC. No further purification
was necessary before injection. The Re(CO)3 complex of one of the fluoroquinolones
(levofloxacin) was synthesized using [Re(CO)3(H2O)3]OTf and Re(CO)5Br precursors in separate
experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies
revealed the formation of a single species in which the piperazinyl nitrogen and the –COOH
group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the
Re(CO)3 core. The HPLC elution pattern and retention time of the Re(CO)3-LVX complex were
comparable to those of the corresponding 99mTc(CO)3-complex proving their similarity. When
incubated in isotonic saline and serum up to 24 h 99mTc(CO)3-labeled fluoroquinolones exhibited
good in vitro stability. Biodistribution studies performed at different time points on rats
intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a
higher uptake in the infected area than the turpentine induced inflamed area. The uptake in
infected thigh was significant with 99mTc(CO)3-OFX followed by 99mTc(CO)3-LVX. The mean
ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h,
respectively, for 99mTc(CO)3-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for
99mTc(CO)3-LVX. The above abscess to muscle ratios were higher than reported for
99mTc-ciprofloxacin and other 99mTc-labeled fluoroquinolones. Scintigraphy studies also showed
a significant uptake in the infectious lesions suggesting that 99mTc(CO)3-fluoroquinolones might
be useful as diagnostic agents for targeted delivery in bacterial infection.
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| Publisher |
The Royal Society of Chemistry
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| Date |
2012
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| Type |
Article
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2521/1/Metallomics%2C_2012%2C_4%2C_1197_(2).pdf
Nayak, Dipak Kumar and Baishya, Rinku and Halder, Kamal Krishna and Sen, Tuhinadri and Sarkar, Bharat R. and Ganguly, Shantanu and Das, M. K and Chatterjee Debnath, Mita (2012) Evaluation of 99mTc(I)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection. Metallomics, 4. pp. 1197-1208. |
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| Relation |
http://dx.doi.org/10.1039/c2mt20132a
http://www.eprints.iicb.res.in/2521/ |
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