7798 A Prospective Within-Patient Comparison of Molecular Imaging Ligands for Detection Of Surgically Curable Primary Aldosteronism (PA), and an Assessment of Accuracy in Cortisol Co-Secretors
Bibliographic record
Abstract
Abstract Disclosure: E. Goodchild: None. X. Wu: None. R. Senanayake: None. J. MacFarlane: None. G. Argentesi: None. K. Laycock: None. C. Cabrera: None. S.M. O'Toole: None. J. Salsbury: None. D. Benu: None. Y. Lee: None. A. Chua: None. M. Mattson: None. P. Laila: None. N. Hilliard: None. M. Alison: None. D. Berney: None. K. Drew: None. C. Mein: None. E. Wozniak: None. J. Kearney: None. A. Sahdev: None. N. Bird: None. G. Smith: None. M. Hird: None. V. Warnes: None. D. Gillett: None. F. Aigbirhio: None. A. McIntosh: None. A. McConnachie: None. K. Cruickshank: None. H. Cheow: None. M. Gurnell: None. W. Drake: None. M.J. Brown: None. Introduction: Molecular imaging could reduce the need for invasive, scarcely-available adrenal sampling (AVS) to identify aldosterone-producing adenomas (APAs). Easily-distributable ligands for widespread use will be needed. Imidazole ligands lacking selectivity ex vivo for CYP11B1 and CYP11B2 are rendered selective in vivo by pre-treatment with dexamethasone. Aims To determine whether post-dexamethasone para-chloro-2-[[1]8F]fluoroethyletomidate PET-CT (CETO) (T ½ 110min), is interchangeable with previously validated [[1][1]C]-metomidate PET-CT (MTO) (T ½ 20min) for the diagnosis of APA. To identify whether a non-fully-suppressed cortisol after prolonged (72h) low-dose dexamethasone forewarns of an increased risk of a false-positive MTO result, in the MATCH study cohort.1Experimental design Prospective within-patient comparison of diagnostic interventions (n=31), with independent scoring of each as high, medium, low probability of unilateral PA, blind to scoring of the other scan or AVS. Prospective measurements of cortisol after prolonged low-dose dexamethasone suppression (PLDDF) and urinary hybrid steroids, with 6-month post-operative PASO biochemical outcomes and APA somatic genotyping when high probability (MTO or AVS) mandated surgery. Major results MTO and CETO agreed in 29/31, kappa=0.85 [95%CI 0.68,1.00]. Scatter was evenly distributed on either side of zero on Bland-Altman analysis (bias -0.04, [95% CI -0.12,0.04]. Of all 174 MATCH-study patients (n=174) PLDDF was available in 156, 32 had PLDDF >25nmol/L. Of these, MTO scored 16 as high probability of unilateral PA, in whom there was complete PASO biochemical success in 14 (88%), and absent in 2 (12%), indicating possible false-positives (AVS had failed in both). In patients with PLDDF </=25nmol/L, MTO identified unilateral disease in 22, 19 (86.3%) of whom had complete biochemical success at 6 months, 3 (13.6%) with partial or absent success. 22 patients had both an elevated PLDDF and urinary hybrid steroid profiles measured, of whom 4 had an elevated 18OH/F ratio. PLDDF in unilateral and not-unilateral MTO outcome were comparable (unpaired T test p= 0.92). A known somatic genotype mutation was found in 21 patients with PLDDF >25nmol/l. PLDDF was highest in KCNJ5 mutants (12/21, mean 55.3nmol/L), compared to ATP1A1 (3/21, mean 44nmol/L), CACNA1D (4/21, mean 31nmol/L), ATP2B3 (1/21, 36nmol/L) and GNAQ (1/21, 28nmol/L). All had complete biochemical success at 6 months post-op. Conclusion: CETO is interchangeable with MTO, which is non-inferior to AVS, in lateralising aldosterone excess in PA patients. False-positives rarely occurred by MTO, and autonomous cortisol secretion did not increase the chance of a false-positive MTO result, compared to patients without, in this cohort. Reference: (1) Wu X et al. Nature Medicine. 2023;29:190-202. Presentation: 6/3/2024
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".