Xiaoyan M Zhang1, Halle H Zhang2, Patrick McLeroth3, Richard D Berkowitz4, Michael A Mont5, Michael G Stabin6, Barry A Siegel7, Abass Alavi8, T Marc Barnett9, Jeffrey Gelb3, Chantal Petit3, John Spaltro3, Steve Y Cho10, Martin G Pomper11, James J Conklin12, Chetan Bettegowda13, Saurabh Saha14. 1. BioMed Valley Discoveries Inc., Kansas City, Missouri. Electronic address: mzhang@biomed-valley.com. 2. BioMed Valley Discoveries Inc., Kansas City, Missouri. 3. Covance, Princeton, New Jersey. 4. Phoenix Clinical Research, Tamarac, Florida. 5. The Rubin Institute for Advanced Orthopedics, Sinai Hospital, Baltimore, Maryland. 6. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee. 7. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. 8. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 9. Mission Hospital, Ashville, North Carolina. 10. Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. 11. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland. 12. ICON Medical Imaging, Warrington, Pennsylvania. 13. Department of Neurology, The Johns Hopkins Medical Institutes, Baltimore, Maryland. 14. BioMed Valley Discoveries Inc., Kansas City, Missouri. Electronic address: ssaha@biomed-valley.com.
Abstract
INTRODUCTION: Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. METHODS: To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). RESULTS: The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. CONCLUSIONS: [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity.
INTRODUCTION:Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. METHODS: To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). RESULTS: The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. CONCLUSIONS: [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity.
Authors: Mark A Sellmyer; Iljung Lee; Catherine Hou; Chi-Chang Weng; Shihong Li; Brian P Lieberman; Chenbo Zeng; David A Mankoff; Robert H Mach Journal: Proc Natl Acad Sci U S A Date: 2017-07-17 Impact factor: 11.205
Authors: Alvaro A Ordonez; Edward A Weinstein; Lauren E Bambarger; Vikram Saini; Yong S Chang; Vincent P DeMarco; Mariah H Klunk; Michael E Urbanowski; Kimberly L Moulton; Allison M Murawski; Supriya Pokkali; Alvin S Kalinda; Sanjay K Jain Journal: J Nucl Med Date: 2016-09-15 Impact factor: 10.057
Authors: Filipa Mota; Alvaro A Ordonez; George Firth; Camilo A Ruiz-Bedoya; Michelle T Ma; Sanjay K Jain Journal: J Med Chem Date: 2020-02-21 Impact factor: 7.446
Authors: Kiyoko Takemiya; Xinghai Ning; Wonewoo Seo; Xiaojian Wang; Rafi Mohammad; Giji Joseph; Jane S Titterington; Colleen S Kraft; Jonathan A Nye; Niren Murthy; Mark M Goodman; W Robert Taylor Journal: JACC Cardiovasc Imaging Date: 2018-04-18
Authors: Ilona Polvoy; Robert R Flavell; Oren S Rosenberg; Michael A Ohliger; David M Wilson Journal: J Nucl Med Date: 2020-08-06 Impact factor: 11.082
Authors: Marjolein Heuker; Anna Gomes; Jan Maarten van Dijl; Gooitzen M van Dam; Alexander W Friedrich; Bhanu Sinha; Marleen van Oosten Journal: Clin Transl Imaging Date: 2016-07-16