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68Ga-DOTA Ubiquicidin PET/CT in an Infected Implant

2017, Clinical Nuclear Medicine

We describe the case of a 55-year-old man who presented with history of fever for 3 months that began 2 months after he had undergone open reduction and internal fixation of left humerus fracture. Implant infection was suspected, but conventional imaging remained unyielding. 68 Ga-DOTA ubiquicidin PET/CT showed increased tracer uptake along the entire length of the implant in the left humerus. Implant removal and temporary external fixation were done. In 24 hours, the patient became afebrile, and blood culture on the fourth day was sterile.

INTERESTING IMAGE 68 Ga-DOTA Ubiquicidin PET/CT in an Infected Implant Arun Sasikumar, MD,* Ajith Joy, DRM,* Raviteja Nanabala, MSc,* M.R.A. Pillai, PhD, DSc,* and Hari T.A., MD† Abstract: We describe the case of a 55-year-old man who presented with history of fever for 3 months that began 2 months after he had undergone open reduction and internal fixation of left humerus fracture. Implant infection was suspected, but conventional imaging remained unyielding. 68GaDOTA ubiquicidin PET/CT showed increased tracer uptake along the entire length of the implant in the left humerus. Implant removal and temporary external fixation were done. In 24 hours, the patient became afebrile, and blood culture on the fourth day was sterile. Key Words: 68Ga-DOTA UBI, infected implant, infection imaging, PET/CT (Clin Nucl Med 2017;42: e115–e116) Received for publication May 10, 2016; revision accepted October 6, 2016. From the *Kerala Institute of Medical Sciences (KIMS)–DDNMRC, KIMS Cancer Centre, and †KIMS Hospital, Trivandrum, Thiruvananthapuram, Kerala, India. Conflicts of interest and sources of funding: none declared. Correspondence to: Arun Sasikumar, MD, KIMS-DDNMRC, KIMS hospital North Block, Anayara PO, Thiruvananthapuram, Kerala 695029, India. E-mail: [email protected]. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/17/4202–e115 DOI: 10.1097/RLU.0000000000001464 REFERENCES 1. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961;40:1–30. 2. Bleeker-Rovers CP, van der Meer JW, Oyen WJ. Fever of unknown origin. Semin Nucl Med. 2009;39:81–87. 3. Love C, Palestro CJ. Nuclear medicine imaging of bone infections. Clin Radiol. 2016;71:632–646. 4. Wenter V, Müller JP, Albert NL, et al. The diagnostic value of [(18)F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection. Eur J Nucl Med Mol Imaging. 2016;43:749–761. 5. Kouijzer IJ, Bleeker-Rovers CP, Oyen WJ. FDG-PET in fever of unknown origin. Semin Nucl Med. 2013;43:333–339. 6. Ostovar A, Assadi M, Vahdat K, et al. A pooled analysis of diagnostic value of (99m)Tc-ubiquicidin (UBI) scintigraphy in detection of an infectious process. Clin Nucl Med. 2013;38:413–416. 7. Hiemstra PS, van der Barselaar MT, Roest M, et al. Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages. J Leukoc Biol. 1999;66:423–428. 8. Tollin M, Bergman P, Svenberg T, et al. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003;24:523–530. 9. Lupetti A, Nibbering PH, Welling MM, et al. Radiopharmaceuticals: new antimicrobial agents. Trends Biotechnol. 2003;21:70–73. 10. Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003;55:27–55. 11. Vilche M, Reyes AL, Vasilskis E, et al. 68Ga-NOTA-UBI-29-41 as a PET tracer for detection of bacterial infection. J Nucl Med. 2016;57:622–627. 12. Ebenhan T, Zeevaart JR, Venter JD, et al. Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging. J Nucl Med. 2014;55:308–314. Clinical Nuclear Medicine • Volume 42, Number 2, February 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. www.nuclearmed.com e115 Sasikumar et al Clinical Nuclear Medicine • Volume 42, Number 2, February 2017 FIGURE 1. We describe the case of a 55-year-old man who presented with history of fever for 3 months that began 2 months after he had undergone open reduction and internal fixation of left humerus fracture. He was complaining of pain and restricted movements at the left shoulder with nonunited fracture of the left humerus. He was in sepsis, and blood cultures repeatedly grew methicillin-sensitive Staphylococcus aureus. Despite 1 week of intravenous sensitive antibiotics, fever persisted. Conventional workup for persistent fever was unyielding, and the search for an obvious source of infection including a transesophageal echocardiogram for vegetations was negative. Implant infection was suspected, but conventional imaging remained unyielding. 68Ga-DOTA ubiquicidin (UBI) PET/CT (A, MIP image; B, fused PET/CT; and C, CT image) was done, which showed increased tracer uptake (SUVmax 4.36) along the entire length of the implant in the left humerus (red arrow). Consequently, implant removal and temporary external fixation were done. In 24 hours, the patient became afebrile, and blood culture on the fourth day was sterile. Fever of unknown origin (FUO) was defined by Petersdorf and Beeson1 as an illness of more than 3 weeks’ duration, fever greater than 38.3°C (101°F) on several occasions, and diagnosis uncertain after 1 week of observation in the hospital. The causes of FUO and the spectrum of diseases contributing to the list of causes of FUO keep changing with time; still approximately 25% of the causes are infective in nature.2 Various imaging options are available in nuclear medicine with respect to infection imaging, but each with its own merits and demerits. In suspected implant infection, nuclear medicine offers imaging from bone scintigraphy to labeled white blood cell imaging.3 18F-FDG PET/CT is useful in detecting implant-associated infections; however, specificity remains debatable.4 Recently, 18F-FDG PET/CT has been suggested as a routine procedure in the workup of patients with FUO5; however, its inadequate specificity poses trouble in implant-associated infection. Studies have shown that 99mTc-UBI has a reasonably high specificity in detecting infection.6 Ubiquicidin is an antimicrobial peptide that protects humans from infiltrating pathogens. It has been postulated that the antimicrobial peptides selectively bind to bacterial cytoplasmic membranes. DOTA acts as a bifunctional chelator for 68Ga labeling. The cationic peptide residues of UBI interact electrostatically with the anionic regions of bacterial membranes.7–10 68 Ga-NOTA UBI as a PET tracer for imaging bacterial infection was found useful in preclinical studies.11,12 In this case, the possibility of imaging bacterial infection with 68Ga-DOTA UBI PET/CT was explored. Owing to the versatile chemistry of 68Ga and relatively easy availability of 68Ge-68Ga generators, preparation of 68Ga-DOTA UBI is not technically challenging. 68Ga-DOTA UBI PET/CT would be an area that is worth exploring because many patients would directly benefit from it, if proven definitely useful in imaging bacterial infections. e116 www.nuclearmed.com © 2016 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.