{"doi":"10.1162/imag_a_00402","title":"Test–retest performance of [18F]MK-6240 tau burden and relative delivery indices in cognitively normal older subjects using PET/MRI","abstract":"Abstract Accurate interpretation of quantitative positron emission tomography (PET) outcomes hinges on understanding the test–retest variability (T-RT). Previous studies of the tau-PET ligand [18F]MK-6240 reported adequate T-RT performance of tau burden estimates over a short-term 21-day and over a longer-term 6-month T-RT period, primarily involving Alzheimer’s disease (AD) and cognitively normal (CN) subjects, respectively. However, several T-RT characteristics have not yet been reported, particularly in older CN (oCN) subjects. Here, we investigate the short-term T-RT performance of dynamic [18F]MK-6240 outcomes in a group largely consisting of oCN. We report T-RT for uptake in potential reference regions, for extracerebral off-target signal, and for estimates of tau burden and relative delivery indices in tau-bearing target regions. Eight participants (7 oCN, 1 AD) underwent baseline dynamic [18F]MK-6240 PET/MRI (Biograph mMR) and a retest follow-up PET/MRI scan within approximately 3 weeks. T-RT was evaluated using absolute percentage differences and intraclass correlation coefficients (ICC) in three groups of regions: (1) potential reference regions using standardized-uptake values 90–110 minutes post-injection (SUV90–110); (2) target regions using SUV ratios (SUVR90–110), distribution volume ratios (DVR), and relative delivery (R1); and (3) extracerebral region using SUVR90–110. A voxel-based partial volume correction (PVC) was applied. T-RT was evaluated with and without PVC. In oCN subjects, the SUV90–110 T-RT in the evaluated reference regions ranged from 6 to 11% (ICC > 0.9); target region T-RT was similar for SUVR90–110 (4–9%, ICC: 0.62–0.97), DVR (3–10%, ICC: 0.66–0.92), and R1 (3–14%, ICC: 0.52–0.97). PVC had minimal impact on reference region SUV90–110 T-RT, but increased target region T-RT variability (SUVR90–110: 10–26%; DVR: 6–22%; R1: 4–20%). Extracerebral SUVR90–110 exhibited higher T-RT variability (~12%, ICC: 0.85) than other target regions (average 6%) and increased to ~15% after PVC. Our findings are consistent with previous reports and provide further evidence of acceptable [18F]MK-6240 T-RT in low-signal oCN subjects. Our results suggest [18F]MK-6240 is suitable for detecting early tau deposition and longitudinal changes over time, and further support the viability of [18F]MK-6240 R1 to evaluate longitudinal changes in perfusion. PVC increased T-RT variability in tau burden and R1 outcomes. Notably, the extracerebral signal exhibited higher T-RT variability than other target and reference regions and may affect their signal.","journal":"Imaging Neuroscience","year":2024,"id":451074,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":862230,"name":"Jessie Fanglu Fu","orcid":"0000-0002-4970-7811","position":1,"is_corresponding":false},{"id":909751,"name":"Andrew N. Salvatore","orcid":null,"position":2,"is_corresponding":false},{"id":1272042,"name":"Arun Garimella","orcid":"0000-0002-5851-9804","position":3,"is_corresponding":false},{"id":1251739,"name":"Derek Huell","orcid":"0000-0002-9658-8800","position":4,"is_corresponding":false},{"id":864238,"name":"Hasan Sari","orcid":"0000-0002-1504-1767","position":5,"is_corresponding":false},{"id":308503,"name":"David Izquierdo‐Garcia","orcid":"0000-0003-0763-8827","position":6,"is_corresponding":false},{"id":236184,"name":"Nathaniel D. Mercaldo","orcid":"0000-0003-1658-6598","position":7,"is_corresponding":false},{"id":19606,"name":"Bradford C. Dickerson","orcid":"0000-0002-5958-3445","position":8,"is_corresponding":false},{"id":232961,"name":"Keith A. Johnson","orcid":"0000-0002-5916-6043","position":9,"is_corresponding":false},{"id":308505,"name":"Ciprian Catana","orcid":"0000-0002-3249-5971","position":10,"is_corresponding":false},{"id":275736,"name":"Julie C. Price","orcid":"0000-0001-7131-4865","position":11,"is_corresponding":false},{"id":679597,"name":"Cristina Lois","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:02:41.417944Z","pmid":"40800311","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":[]}