Journal of Labelled Compounds and Radiopharmaceuticals J Label Compd Radiopharm 2007; 50: 25–31. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.1153 JLCR Research Article Technetium-99m labeling and freeze-dried kit formulation of levofloxacin (L-Flox): A novel agent for detecting sites of infection E. A. EL-GHANY 1, *, A. M. AMIN 1 , O. A. EL-KAWY 1 and MAGDY AMIN 2 1 Labeled Compound Department, Hot Lab. Center, Atomic Energy Authority, P.O. Box. 11787, Cairo, Egypt 2 Faculty of Pharmacy, Cairo University, Cairo, Egypt Received 28 August 2006; Revised 10 October 2006; Accepted 11 October 2006 Abstract: In this study, the labeling method of levofloxacin with technetium-99m and its biological evaluation were described. 99m Tc-L-Flox was synthesized via direct complexation with technetium-99m in the presence of stannous chloride dihydrate as reducing agent. The optimum amounts of the reactants are: 1–2 mg levofloxacin, 150 mg stannous chloride dihydrate and 48–1490 MBq pertechnetate. The reaction mixture was bring to pH 6 and kept at room temperature for 30 min. The labeled levofloxacin was stable for more than 8 h. The in vivo evaluation of 99m Tc- L-Flox in man-induced inflammation models showed that this tracer was localized with different values. The live E. Coli model had the highest value which was 2.9%, the heat killed E. coli model had a value of 2.0%, and the turpentine oil model had a value of 1.2% at 24 post injection, while the non-inflamed muscle had activity of 0.5%. All the gathered biological data support the usefulness of 99m Tc-L-Flox as infection imaging agent. The freeze-dried form of Sn-L-Flox was prepared and found meet all the radiochemical and biological tests. Copyright # 2007 John Wiley & Sons, Ltd. Keywords: fluoroquinolones; technetium-99m; infections; freeze-drying Introduction Quinolone drugs are large and widely used class of synthetic antibacterial compounds. 1–3 First generation quinolones include naldexic acid and oxolinic acid. Subsequent generations have been modified to in- crease spectrum and potency. The most significant modification has been the addition of a fluorine atom at position C6 in drugs such as levofloxacin. Levofloxacin shown in Figure 1 is the 4th generation of quinolone antibiotics that has activity against a wide range of Gram-negative and Gram-positive microorganisms in- cluding Streptococcus pneumoniae multidrug-resistant strains. Levofloxacin showed widespread distribution into body tissues and it was stereochemically stable in plasma and urine. Levofloxacin undergoes limited metabolism in humans and excreted as unchanged drug in the urine that used safely in patients with impaired renal functions and hepatic insufficiency. Quinolones target bacterial type topoisomerase II ‘DNA gyrase’ in Gram-negative bacteria and DNA topoisome- rase IV in Gram-positive bacteria. 2 Infection is a major cause of mortality and morbidity in the world. The appearance of multidrug-resistant bac- teria required a more advanced imaging technique. Nuclear medicine techniques are used in the context of infection localization. Inflammation imaging agents such as polyclonal and monoclonal antibodies, peptides, 4–6 cytokines, 7 and HMPAO-leukocytes 8,9 cannot discrimi- nate between septic and sterile inflammatory sites. A novel approach using a bacterially binding radiola- beled antimicrobial agent to detect infections was introduced since 1996 by Vinjamuri and Co-workers 10 when they labeled ciprofloxacin with technetium-99m, and clinically used under the trade name ‘Infecton’. Later, many fluoroquinolones antimicrobial agents were labeled with technetium-99m and evaluated as infection imaging agents. 11 During this study, levofloxacin was labeled with technetium-99m and the parameters affect- ing this labeling reaction were studied. The labeled levofloxacin was evaluated biologically in normal and in inflamed mice. A freeze-dried form of Sn-L-Flox was prepared and evaluated radiochemically and biologically. *Correspondence to: E. A. El-Ghany, Atomic Energy Authority, Cairo, 11787, Egypt. E-mail: abdelghanyea@yahoo.com Copyright # 2007 John Wiley & Sons, Ltd.