Synthesis of the Novel AT<sub>1</sub> Receptor Tracer [<sup>18</sup>F]Fluoropyridine–Candesartan via Click Chemistry
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide A novel 7-((4-(3-((2-[ 18 F]fluoropyridin-3-yl)oxy)propyl)-1 H -1,2,3-triazol-1-yl)methyl)-1 H -benzo[ d ]imidazole derivative of the angiotensin II type-1 receptor (AT 1 R) blocker candesartan, [ 18 F]fluoropyridine–candesartan, was synthesized via the copper-catalyzed azide–alkyne cycloaddition click reaction between 2-[ 18 F]fluoro-3-(pent-4-yn-1-yloxy)pyridine ([ 18 F]FPyKYNE) and the tetrazole-protected azido-candesartan derivative, followed by acid deprotection. This three-step, two-pot, and two-step purification synthesis was done within 2 h. The use of tris[(1-hydroxypropyl-1 H -1,2,3-triazol-4-yl)methyl]amine (THPTA) as a Cu(I) stabilizing agent increased the overall radiochemical yield by 4-fold (10 ± 2%, n = 13) compared to the reaction without THPTA (2.4 ± 0.2%, n = 3; decay-corrected from 18 F produced at the end-of-beam). Complete separation of [ 18 F]FPyKYNE from its nitro precursor and [ 18 F]fluoropyridine–candesartan from the deprotected azido-candesartan allowed for high molar activities (>380 GBq/μmol) of the tracer. The use of 0.1% trifluoroacetic acid in water for reformulation and the addition of sodium ascorbate to the final formulation (1.6 ± 0.2 GBq/mL, n = 3) prevented tracer radiolysis with >97% radiochemical purity for a period of up to 10 h after the end-of-synthesis. A significant reduction in the uptake (86 ± 3%, n = 8) of the tracer was observed ex vivo in rats (at 20 min postinjection) in the AT 1 R-rich kidney cortex following pretreatment with saturating doses of the AT 1 R antagonist candesartan or losartan. This specific binding to AT 1 R was confirmed in vitro in the rat renal cortex (autoradiography) by a reduction of 26 ± 5% ( n = 12) with losartan coincubation (10 μM). These favorable binding properties support further studies to assess the potential of [ 18 F]fluoropyridine–candesartan as a tracer for the positron emission tomography imaging of renal AT 1 R.
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".