Efficacy of 99mTc-Ciprofloxacin and 67Ga-Citrate scintigraphy to discriminate infection foci induced by Staphylococcus aureus from sterile inflammation induced by Carrageenan in rat

Document Type : Original Article

Authors

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

2 Nuclear Science Research School, Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran, Tehran Iran

3 Nuclear Medicine Department, Golestan General Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Introduction: This study was launched to evaluate the sensitivity and specificity of 99mTc-Ciprofloxacin to distinguish infection foci induced by staphylococcus aureus and inflammation lesions induced by carrageenan in the rat foot in comparison with 67Ga-Citrate scintigraphy.
Methods: The labeling and quality control of 99mTc-Ciprofloxacin kits have been performed according to the manufacturer’s instructions. A total number of 40 adult, male NMRI rats were randomly divided into two equal groups, one group for 99mTc-Ciprofloxacin and the other group for 67Ga-Citrate scintigraphy. Every group was subdivided into two groups equally. Septic lesion was induced by Staphylococcus aureus. Aseptic inflammation lesion was induced by carrageenan in the rat foot in the other group. The 99mTc-Ciprofloxacin and 67Ga-Citrate scintigraphy studies have been performed to evaluate the efficacy of radiotracers.
Results: The images showed 67Ga uptake at the infection and inflammation sites. The infection foci could be visualized by 99mTc-Ciprofloxacin scintigraphy due to selective binding of ciprofloxacin to DNA gyrase of bacteria. The inflammation sites have been observed by non-specific uptake of 99mTc-Ciprofloxacin. None of both imaging studies have shown preferentially diagnosis of septic and aseptic inflammation lesions. The sensitivity, specificity and positive predictive value of both scintigraphic techniques were 100%, 50% and 50%, respectively.

Conclusion: The 99mTc-Ciprofloxacin scintigraphy is sensitive for visualization of the lesion, but it could to discriminate between septic and aseptic inflammation lesions. Other modalities must be considered for interpretation of images obtained by 99mTc-Ciprofloxacin scintigraphy.

Main Subjects


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.
Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med. 1994 Apr;24(2):128-41.
Crerand S, Dolan M, Laing P, Bird M, Smith ML, Klenerman L. Diagnosis of osteomyelitis in neuropathic foot ulcers. J Bone Joint Surg Br. 1996 Jan;78(1):51-5.
Bohchelian HA, Klisarova AD, Koeva LA. Radioimmune imaging of diabetic foot infection - Tc-99m-labelled antigranulocyte antibody in combination with Tc-99m-methylene diphosphonate bone scintigraphy. Turk J Med Sci. 2002;32:255-59.
Weiner RE, Thakur ML. Radiolabeled peptides in diagnosis and therapy. Semin Nucl Med. 2001 Oct;31(4):296-311.
Mirshojaei  SF, Gandomkar  M, Najafi  R, Sadat Ebrahimi  SE, Babaei  MH, Shafiei  A, Talebi MH. Radio labeling, quality control and biodistribution of 99m Tc-cefotaxime as an infection imaging agent.  J Radioanal Nucl Chem . 2011;287:21-25.
Shah SQ, Rafiullah Khan M. Radiocharacterization of the 99m Tc–rufloxacin complex and biological evaluation in Staphylococcus aureus infected rat model. J Radioanal Nucl Chem. 2011;288:373-78.
Motaleb MA. Preparation and biodistribution of 99m Tc-lomefloxacin and 99m Tc-ofloxacin complexes. J Radioanal  Nucl Chem. 2007;272:95-99.
Benitez A, Roca M, Martin-Comin J. Labeling of antibiotics for infection diagnosis. Q J Nucl Med Mol Imaging. 2006 Jun;50(2):147-52.
Erfani M, Doroudi A, Hadisi L, Andishmand A, Mirshojaei SF, Shafiei M. (99m) Tc-tricabonyl labeling of ofloxacin and its biological evaluation in Staphylococcus aureus as an infection imaging agent. J Labelled Comp Radiopharm. 2013 Oct;56(12):627-31.
Erfani  M , Doroudi  A, Hadisi  L, Andishmand A, Mazidi SM. Optimization condition in labeling of Ofloxacin with 99mTc and its biological evaluation in Staphylococcus aureus and Escherichia coli for infection imaging. Iran J  Nucl Med. 2013;21(1):1-6.
Fuster D, Soriano A, Garcia S, Piera C, Suades J, Rodríguez D, Martinez JC, Mensa J, Campos F, Pons F. Usefulness of 99mTc-ciprofloxacin scintigraphy in the diagnosis of prosthetic joint infections.  Nucl Med Commun. 2011 Jan;32(1):44-51.
Yapar Z, Kibar M, Yapar AF, Toğrul E, Kayaselçuk U, Sarpel Y. The efficacy of technetium-99m ciprofloxacin (Infecton) imaging in suspected orthopaedic infection: a comparison with sequential bone/gallium imaging.  Eur J Nucl Med. 2001 Jul;28(7):822-30.
Singh B, Mittal BR, Bhattacharya A, Aggarwal A, Nagi ON, Singh AK. Technetium-99m ciprofloxacin imaging in the diagnosis of postsurgical bony infection and evaluation of the response to antibiotic therapy: A case report. J Orthop Surg (Hong Kong). 2005 Aug;13(2):190-4.
Hall AV, Solanki KK, Vinjamuri S, Britton KE, Das SS. Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection. J Clin Pathol. 1998 Mar;51(3):215-9.
Thomson AW, Fowler EF. Carrageenan: a review of its effects on the immune system. Agents Actions. 1981 May;11(3):265-73.
Britton KE, Wareham DW, Das SS, Solanki KK, Amaral H, Bhatnagar A, Katamihardja AH, Malamitsi J, Moustafa HM, Soroa VE, Sundram FX, Padhy AK. Imaging bacterial infection with (99m)Tc-ciprofloxacin (Infecton). J Clin Pathol. 2002 Nov;55(11):817-23.
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.
Sugishita E, Amagaya S, Ogihara Y. Anti-inflammatory testing methods: comparative evaluation of mice and rats. J Pharmacobiodyn. 1981 Aug;4(8):565-75.
Henriques MG, Silva PM, Martins MA, Flores CA, Cunha FQ, Assreuy-Filho J, Cordeiro RS. Mouse paw edema. A new model for inflammation?  Braz J Med Biol Res. 1987;20(2):243-9.
Petersson M, Wiberg U, Lundeberg T, Uvnäs-Moberg K. Oxytocin decreases carrageenan induced inflammation in rats. Peptides. 2001 Sep;22(9):1479-84.
Cuzzocrea S, Sautebin L, De Sarro G, Costantino G, Rombolà L, Mazzon E, Ialenti A, De Sarro A, Ciliberto G, Di Rosa M, Caputi AP, Thiemermann C. Role of IL-6 in the pleurisy and lung injury caused by carrageenan. J Immunol. 1999 Nov 1;163(9):5094-104.
Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT, Currie MG. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol. 1996 Jun;118(4):829-38.
Love C, Palestro CJ. Radionuclide imaging of infection. J Nucl Med Technol. 2004 Jun;32(2):47-57.
Rodriguez-puig D, Piera C, Fuster D, Soriano A, Sierra JM, Rubi S, Saudes  J. A new method of  [99mTc]-ciprofloxacin preparation and quality control. J Labelled Comp Radiopharm. 2006;49(13):1171-1176.
Easmon CS, Crane JP, Blowers A. Effect of ciprofloxacin on intracellular organisms: in-vitro and in-vivo studies. J Antimicrob Chemother. 1986 Nov;18 Suppl D:43-8.