Evaluation of 99mTc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection

Dipak Kumar Nayak; Rinku Baishya; Kamal Krishna Halder; Tuhinadri Sen; Bharat R. Sarkar; Shantanu Ganguly; M. K. Das; Mita Chatterjee Debnath

doi:10.1039/c2mt20132a

Evaluation of ^99mTc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection

Dipak Kumar Nayak, Rinku Baishya, Kamal Krishna Halder, Tuhinadri Sen, Bharat R. Sarkar, Shantanu Ganguly, M. K. Das, Mita Chatterjee Debnath

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

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(H ₂O)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.

Original language	English
Pages (from-to)	1197-1208
Number of pages	12
Journal	Metallomics
Volume	4
Issue number	11
DOIs	https://doi.org/10.1039/c2mt20132a
State	Published - 1 Jan 2012
Externally published	Yes

ASJC Scopus subject areas

Chemistry (miscellaneous)
Biophysics
Biomaterials
Biochemistry
Metals and Alloys

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10.1039/c2mt20132a

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@article{9f2ed43a8e17437d807b36d1f45a6e18,

title = "Evaluation of 99mTc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection",

abstract = "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(H 2O)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.",

author = "Nayak, {Dipak Kumar} and Rinku Baishya and Halder, {Kamal Krishna} and Tuhinadri Sen and Sarkar, {Bharat R.} and Shantanu Ganguly and Das, {M. K.} and Debnath, {Mita Chatterjee}",

year = "2012",

month = jan,

day = "1",

doi = "10.1039/c2mt20132a",

language = "English",

volume = "4",

pages = "1197--1208",

journal = "Metallomics",

issn = "1756-5901",

publisher = "Oxford University Press",

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T1 - Evaluation of 99mTc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection

AU - Nayak, Dipak Kumar

AU - Baishya, Rinku

AU - Halder, Kamal Krishna

AU - Sen, Tuhinadri

AU - Sarkar, Bharat R.

AU - Ganguly, Shantanu

AU - Das, M. K.

AU - Debnath, Mita Chatterjee

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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(H 2O)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.

AB - 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(H 2O)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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SN - 1756-5901

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Evaluation of ^99mTc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection

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