Radiolabeling of Ciprofloxacin with Technetium-99m, Quality Control and Biodistribution

Mirshojaei, S.F; Erfani (Gandomkar), M; Talebi, M.H; Mazidi, M

Radiolabeling of Ciprofloxacin with Technetium-99m, Quality Control and Biodistribution

Document Type : Research Paper

Authors

S.F Mirshojaei

M Erfani (Gandomkar)

M.H Talebi

M Mazidi

Abstract

Radiolabeled antibiotics are used for the specific diagnosis of infection by exploiting their specific binding properties to the bacterial components, thereby making it possible to differentiate infection from sterile lesions. ^99mTc-ciprofloxacin is the most widely used infection imaging agent which belongs to quinolones group and has a vast antimicrobial action against bacterias. Ciprofloxacin binds to bacterial DNA Gyrase and inhibits its conventional synthesis. Ciprofloxacin labeled with ^99mTc specifically binds to various bacteria. Thus, it potentially constitutes a specific marker allowing discrimination between septic and aseptic diseases. In this paper, we describe the labeling of ciprofloxacin with the most widely used imaging radionuclide, ^99mTc. The quality control procedure using thin layer chromatography and the stability of labeled compound and also the effect of different parameters such as pH and stannous chloride amount on the radiolabeling yield were investigated. The maximum radiochemical yield was 90±3%. The stability of the radiolabeled antibiotic in the presence of human serum was about 84.2% and 79.6%, respectively after 1h and 4h. 75% of the activity binds to the plasma proteins and the ratio of infected muscle to non-infected muscle is 3.2 and 1.8, 1h and 4 hours post injection.

Highlights

K.E. Britton, D.W. Wareham, K.K. Solanki, H. Amaral, A. Bhatnagar, “Imaging bacterial infection with ^99mTc-ciprofloxacin (infecton),” J. Clin. Pathol., 55: 817-23 (2008).
D. Wareham, J. Michael, “Advances in bacterial specific imaging,” Braz. Arch. Biol Tech, 48: 145-52 (2005).
S.S. Das, A.V. Hall, D.W. Wareham, K.E. Britton, “Infection imaging with radiopharmaceuticals in the 21^st century,” Braz. Arch, Biol Tech, 45: 25-37 (2002).
K. Sonmezuglu, et al, “Usefulness of ^99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with ^99mTc-HMPAO leukocyte scintigraphy,” J. Nucl. Med., 42: 567-74 (2001).
N. Bhardwaj, A. Bhatnagar, A.K. Singh, “Development and evaluation of a single vial cold kit for infection imaging: Tc-⁹⁹m ciprofloxacin,” World, J. Nucl. Med., 4: 244-251 (2005).
A. Benitez, M. Roca, J. Martin-Comin, “Labeling of antibiotics for infection diagnosis,” Q. J. Nucl. Med. Mol. Imaging, 50: 147-52 (2006).
S. Jun Oh, J. Ryu, J. Woo Shin, E. Jin Yoon, “Synthesis of ⁹⁹mTc-ciprofloxacin by different methods and its biodistribution,” Appl. Rad & Isotopes, 57, 193-200 (2002).
R.H. Siaen, H.J. Rennen, O.C. Boermann, R. Dierckx, G. Slegers, “Synthesis and comparison of ⁹⁹mTc-enrofloxacin and ⁹⁹mTc-ciprofloxacin,” J. Nucl. Med 45; 2088-2094 (2004).
B. Singh, B.R. Mittal, A. Bhattacharya, “Tc-99m ciprofloxacin imaging in the diagnosis of postsurgical bony infection and evaluation of the response to antibiotic therapy,” J. of Orthopedic Surgery, 13(2): 190-194 (2005).

Keywords

Radiopharmaceuticals

Ciprofloxacin

Radiolabeling

Infection Detection

Technetium 99m

1. K.E. Britton, D.W. Wareham, K.K. Solanki, H. Amaral, A. Bhatnagar, “Imaging bacterial infection with ^99mTc-ciprofloxacin (infecton),” J. Clin. Pathol., 55: 817-23 (2008).
2. D. Wareham, J. Michael, “Advances in bacterial specific imaging,” Braz. Arch. Biol Tech, 48: 145-52 (2005).
3. S.S. Das, A.V. Hall, D.W. Wareham, K.E. Britton, “Infection imaging with radiopharmaceuticals in the 21^st century,” Braz. Arch, Biol Tech, 45: 25-37 (2002).
4. K. Sonmezuglu, et al, “Usefulness of ^99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with ^99mTc-HMPAO leukocyte scintigraphy,” J. Nucl. Med., 42: 567-74 (2001).
5. N. Bhardwaj, A. Bhatnagar, A.K. Singh, “Development and evaluation of a single vial cold kit for infection imaging: Tc-⁹⁹m ciprofloxacin,” World, J. Nucl. Med., 4: 244-251 (2005).
6. A. Benitez, M. Roca, J. Martin-Comin, “Labeling of antibiotics for infection diagnosis,” Q. J. Nucl. Med. Mol. Imaging, 50: 147-52 (2006).
7. S. Jun Oh, J. Ryu, J. Woo Shin, E. Jin Yoon, “Synthesis of ⁹⁹mTc-ciprofloxacin by different methods and its biodistribution,” Appl. Rad & Isotopes, 57, 193-200 (2002).
8. R.H. Siaen, H.J. Rennen, O.C. Boermann, R. Dierckx, G. Slegers, “Synthesis and comparison of ⁹⁹mTc-enrofloxacin and ⁹⁹mTc-ciprofloxacin,” J. Nucl. Med 45; 2088-2094 (2004).
9. B. Singh, B.R. Mittal, A. Bhattacharya, “Tc-99m ciprofloxacin imaging in the diagnosis of postsurgical bony infection and evaluation of the response to antibiotic therapy,” J. of Orthopedic Surgery, 13(2): 190-194 (2005).