[(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.

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.

Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.

Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.