{"doi":"10.1021/acsinfecdis.4c00487","title":"<scp>d</scp>-[5-<sup>11</sup>C]-Glutamine Positron Emission Tomography Imaging for Diagnosis and Therapeutic Monitoring of Orthopedic Implant Infections","abstract":"Orthopedic implant infections (OIIs) present diagnostic and therapeutic challenges, owing to the lack of methods to distinguish between active infection and sterile inflammation. To address this unmet need, d -amino-acid-based radiotracers with unique metabolic profiles in microorganisms have emerged as a novel class of infection-specific imaging agents. Given the pivotal role of d -glutamine in bacterial biofilm formation and virulence, herein, we explored the potential of positron emission tomography (PET) imaging with d -[5- 11 C]-Glutamine ( d -[5- 11 C]-Gln) for early detection and treatment monitoring of OIIs. In vitro studies confirmed an active uptake of d -[5- 11 C]-Gln by Staphylococcus aureus ( S. aureus ) biofilm commonly associated with OIIs. In vivo evaluations included PET imaging comparisons with d -[5- 11 C]-Gln vs l -[5- 11 C]-Gln or 2-deoxy-2-[ 18 F]-fluoroglucose ([ 18 F]-FDG) in a rat OII model with tibial implantation of sterile or S. aureus - colonized stainless-steel screws before and after treatment. These studies demonstrated that the uptake of d -[5- 11 C]-Gln was significantly higher in the infected screws than that in sterile screws (∼3.4-fold, p = 0.008), which displayed significantly higher infection-to-background muscle uptake ratios (∼2-fold, p = 0.011) with d -[5- 11 C]-Gln as compared to l -[5- 11 C]-Gln. Following a 3 week vancomycin treatment, imaging with d -[5- 11 C]-Gln showed a significant reduction in uptake at the infected sites (∼3-fold, p = 0.0008). Further regression analyses revealed a superior correlation of residual infection-associated radiotracer uptake with the postimaging ex vivo bacterial counts for d -[5- 11 C]-Gln ( k = 0.473, R 2 = 0.796) vs [ 18 F]-FDG ( k = 0.212, R 2 = 0.434), suggesting that d -[5- 11 C]-Gln PET had higher sensitivity for detecting residual bacterial burden than [ 18 F]-FDG PET. Our results demonstrate the translational potential of d -[5- 11 C]-Gln PET imaging for noninvasive detection and treatment monitoring of OIIs.","journal":"ACS Infectious Diseases","year":2024,"id":451859,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":276891,"name":"Aditi Mulgaonkar","orcid":"0000-0002-2943-5628","position":1,"is_corresponding":false},{"id":1273253,"name":"Ning Zhou","orcid":"0000-0002-8967-3468","position":2,"is_corresponding":false},{"id":270968,"name":"Tam Nguyen","orcid":"0000-0002-8338-7436","position":3,"is_corresponding":false},{"id":1273741,"name":"Shelby Freedman Harris","orcid":null,"position":4,"is_corresponding":false},{"id":638468,"name":"Amber Sherwood","orcid":"0000-0003-2211-8504","position":5,"is_corresponding":false},{"id":904315,"name":"Vicki Ea","orcid":"0000-0002-5450-6264","position":6,"is_corresponding":false},{"id":1273254,"name":"Katie Rubitschung","orcid":"0009-0009-3383-6609","position":7,"is_corresponding":false},{"id":1273255,"name":"Laila M Castellino","orcid":"0000-0002-3184-4850","position":8,"is_corresponding":false},{"id":527047,"name":"Orhan K. Öz","orcid":"0000-0002-5846-6829","position":9,"is_corresponding":false},{"id":276892,"name":"Xiankai Sun","orcid":"0000-0002-5140-6110","position":10,"is_corresponding":false},{"id":283904,"name":"Liping Tang","orcid":"0000-0002-3393-7073","position":11,"is_corresponding":false},{"id":499888,"name":"Cynthia M. Co","orcid":"0000-0002-5779-5444","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:45.951080Z","pmid":"39410659","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}