Radiocomplexation and biological evaluation of nemonoxacin in mice infected with multiresistant Staphylococcus aureus and penicillin-resistant Streptococci O. A. El-Kawy 1 • K. Farah 1 Received: 4 December 2014 / Published online: 21 March 2015 Ó Akade ´miai Kiado ´, Budapest, Hungary 2015 Abstract In the current investigation nemonoxacin (NMX) was radiolabeled with 99m Tc in the presence of stannous chloride dihydrate as reducing agent. Factors af- fecting the percent labeling yield of 99m Tc-Nemonoxacin ( 99m Tc-NMX) complex were studied in details. The labeled compound was radiochemically characterized and was stable for a time up to 4 h. The complex showed in vitro saturated binding with living multiresistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococci (PRSC). Biodistribution and imaging studies were per- formed. All results showed that 99m Tc-NMX complex is a promising agent for MRSA and PRSC infection imaging and can differentiate between infected and sterile inflammations. Keywords Nemonoxacin Á 99m Tc Á Infection Á Inflammation Introduction The role of bacterial infection in the existing high rate of morbidity and mortality is still a serious concern of the clinician for its early diagnosis and timely management with appropriate drug [1, 2]. In spite of the innovation in the diagnostic facilities, imaging of infection is still a se- rious concern of the medical community. The role of the advanced diagnostic facilities like computerized tomogra- phy (CT) and magnetic resonance imaging (MRI) has proven inadequate in the diagnosis of infection and its discrimination from inflammation in the early stages [3–5]. Recently a number of novel 99m Tc labeled antibiotics have been reported as promising radiotracers for the diagnosis of infection and its discrimination from inflammation [6–9]. However these labeled antibiotics face the growing prob- lem of microbial resistance which results in false-negative results [10] forcing us to keep on searching for newer and better antibiotics and infection imaging agents. Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone with remarkably enhanced in vitro and in vivo activity against a wide variety of clinically relevant Gram- positive, Gram-negative, and atypical pathogens [11, 12], especially gram-positive bacteria, such as penicillin- and quinolone-resistant Streptococcus pneumoniae and methi- cillin- and vancomycin-resistant Staphylococcus aureus [13, 14]. The addition of a methoxy group at the C-8 po- sition (Fig. 1) enables nemonoxacin to target both topoi- somerase IV and topoisomerase II, associated with an improved spectrum of activity and reduced mutant selection compared to other fluoroquinolones. Bacteria become re- sistant to nemonoxacin only when three different mutations occur in their quinolone resistance-determining regions (QRDR) of genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) [15, 16]. In addition, the removal of the fluorine residue reduces the incidence of toxic side effects [14]. In the current investigation nemonoxacin was labeled with 99m Tc. Factors affecting the labeling yield were studied. The 99m Tc-Nemonoxacin ( 99m Tc-NMX) complex was characterized in terms of radiochemical stability in saline, in vitro stability in serum, in vitro binding with living and heat killed multiresistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococci (PRSC) and biodistribution in artificially living MRSA and PRSC in- fected mice. & O. A. El-Kawy elkawyo@gmail.com 1 Labelled Compounds Department, Atomic Energy Authority, Cairo 13759, Egypt 123 J Radioanal Nucl Chem (2015) 306:123–130 DOI 10.1007/s10967-015-4069-6 Author's personal copy