Optimization condition in labeling of Ofloxacin with 99mTc and its biological evaluation in Staphylococcus aureus and Escherichia coli for infection imaging

Document Type : Original Article


1 Nuclear Science Research School, Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran, Tehran, Iran

2 School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


Introduction: The use of radiopharmaceuticals is a powerful tool in the management of patients with infectious or inflammatory diseases in nuclear medicine. In this study ofloxacin as a second-generation fluoroquinolone is used to design a desired infection imaging agent after labeling with 99mTc via direct labeling. Methods: Ofloxacin was radiolabeled with 99mTc using different concentrations of ligand, stannous chloride, sodium pertechnetate and at different pH. Then labeling yield, stability in saline and serum, lipophilicity, binding with Staphylococcus aureus and Escherichia coli and biodistribution in infected mice for labeled compound were studied. Results: The final complex was characterized by TLC and HPLC and radiochemical purity of >90% was obtained when 1.5 mg ofloxacin in presence of 75 µg SnCl2 was labeled with 370 MBq sodium pertechnetate. The complex showed specific binding to Staphylococcus aureus and Escherichia coli. Biodistribution results showed that radioligand had high affinity in the infected site in mice. The uptake for Staphylococcus aureus induced infections (T/NT = 2.33 ± 0.17 at 1 h post injection) was higher than that was for Escherichia coli (T/NT = 1.96 ± 0.13 at 1 h post injection). Conclusion: This complex may lead to further development of a radiotracer for imaging of infections induced by gram-positive or gram-negative bacteria.


Main Subjects

Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med. 1994 Apr;24(2):128-41.
Peters AM. The utility of [99mTc]HMPAO-leukocytes for imaging infection. Semin Nucl Med. 1994 Apr;24(2):110-27.
Cardoso VN, Plaza PJ, Roca M, Armero F, Martín-Comin J. Assessment of inflammatory bowel disease by using two different (99m)Tc leucocyte labelling methods. Nucl Med Commun. 2002 Aug;23(8):715-20.
Segura AB, Muñoz A, Brulles YR, Hernandez Hermoso JA, Díaz MC, Bajen Lazaro MT, Martín-Comín J. What is the role of bone scintigraphy in the diagnosis of infected joint prostheses? Nucl Med Commun. 2004 May;25(5):527-32.
Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002 Jan 24;415(6870):389-95.
Welling MM, Nibbering PH, Paulusma-Annema A, Hiemstra PS, Pauwels EK, Calame W. Imaging of bacterial infections with 99mTc-labeled human neutrophil peptide-1. J Nucl Med. 1999 Dec;40(12):2073-80.
Gandomkar M, Najafi R, Mazidi M, Mirfallah SH, Goudarzi M. Three different procedures in labeling of Ubiquicidin with technetium 99m: a comparative study. Iran J Radiat Res. 2009;7(2):97-104.
Gandomkar M, Najafi R, Mazidi M, Goudarzi M, Mirfallah SH. New peptide based freeze-dried kit [99mTc-HYNIC]-UBI 29-41 as a human specific infection imaging agent. Iran J Nucl Med. 2008;16(1):25-30.
Gandomkar M, Najafi R, Shafiei M, Mazidi M, Goudarzi M, Mirfallah SH, Ebrahimi F, Heydarpor HR, Abdie N. Clinical evaluation of antimicrobial peptide [(99m)Tc/Tricine/HYNIC(0)]ubiquicidin 29-41 as a human-specific infection imaging agent. Nucl Med Biol. 2009 Feb;36(2):199-205.
Fournier B, Zhao X, Lu T, Drlica K, Hooper DC. Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus: different patterns of quinolone-induced inhibition of DNA synthesis. Antimicrob Agents Chemother. 2000 Aug;44(8):2160-5.
Mirshojaei SF, Erfani M, Ebrahimi SES, Talebi MH, Haj Hassan Abbasi F. Freeze-dried cold kit for preparation of 99mTc-ciprofloxacin as an infection imaging agent. Iran J Nucl Med. 2010;18(2):45-51.
Britton KE, Vinjamuri S, Hall AV, Solanki K, Siraj QH, Bomanji J, Das S. Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection. Eur J Nucl Med. 1997 May;24(5):553-6.
Mirshojaei SF, Gandomkar M, Najafi R, Ebrahimi SES, Babaei MH, Shafiei A, Talebi MH. Radio labeling, quality control and biodistribution of 99mTc-cefotaxime as an infection imaging agent. J Radioanal Nucl Chem. 2011; 287:21-25.
Vinjamuri S, Hall AV, Solanki KK, Bomanji J, Siraj Q, O'Shaughnessy E, Das SS, Britton KE. Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection. Lancet. 1996 Jan 27;347(8996):233-5.
Solanki KK, Bomanji J, Siraj QH, Small M, Britton KE. Tc-99m Infecton: A new class of radiopharmaceutical for imaging infection. J Nucl Med. 1993;34(Suppl):119P.
Sarda L, Crémieux AC, Lebellec Y, Meulemans A, Lebtahi R, Hayem G, Génin R, Delahaye N, Huten D, Le Guludec D. Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and sterile osteoarticular diseases. J Nucl Med. 2003 Jun;44(6):920-6.
Jurisson S, Berning D, Jia W, Ma D. Coordination compounds in nuclear medicine. Chem Rev. 1993;93(3):1137-56.
Motaleb MA. Preparation and biodistribution of 99mTc-lomefloxacin and 99mTc-ofloxacin complexes. J Radioanal Nucl Chem. 2007;272:95-99.
Sing AK, Bhatnagar A, Singh T, Mathew TL. A process for preparation of technetium 4-fluoroquinolone metallic complexes. Indian Patent Filed. 2001 May; Patent No. 195854.
Bhardwaj N, Bhatnagar A, Singh AK. Development and evaluation of a single vial cold kit for infection imaging: Tc-99m ciprofloxacin. World J Nucl Med. 2005;4:244-51.