P1‐392: Synthesis and evaluation of [18F]fluorinated triazole‐derivatives of the pittsburgh compound as potential PET radiotracers for imaging amyloid plaques
Bibliographic record
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease whose prevalence increases dramatically after the age of 65 years. The presence of β-amyloid plaques in the brain is a pathological feature of the disease. It is difficult to diagnose early stages of AD and to distinguish it from decline in cognitive function associated with memory loss due to the normal aging process. Neuron-imaging techniques, such as PET, play important role in diagnosis of the disease. Therefore, PET imaging probes with high affinity for β-amyloid plaques, capable of detecting low plaque load, are essential in application of PET imaging for presymptomatic identification of patients and monitoring drug treatment. We report progress on the synthesis and in vivo biodistribution of 18F-labeled triazole derivatives of the Pittsburgh compound as potential β-amyloid plaque imaging agents. 2-(4'-azidophenyl)-6-hydroxybenzothiazole was prepared from 2-(4'-nitrophenyl)-6-methoxybenzothiazole by first reducing the nitro to amino to 2-(4'-aminophenyl)-6-methoxybenzothiazole form then deprotecting and finally conversion of the amino to azide. The azide was then reacted with a variety of terminal alkynes under Click conditions using copper (II) sulfate / ascorbic acid as catalyst to form the target triazole-derivative of the Pittsburgh compound. The same azide will be reacted with [18F]fluorinated alkynes to form radiolabeled triazole derivatives of the Pittsburgh compound. In vitro binding affinity will be determined using [125I]IMPY competition experiment using aggregated Aβ(1-42)-peptide. The biodistribution in normal mice will be done by injecting a solution of 3.7MBq of the [18F]fluoro-triazole-derivative in saline containing 10% ethanol. 2-(4'-Azidophenyl)-6-methoxybenzothiazole was successfully synthesized from 2-(4'-aminophenyl)-6- methoxybenzothiazole in a reasonable yield of 43%. The azide was reacted with 3-phenyl-1-propyne and 4-pentyn-1-ol using copper (II) sulfate / ascorbic acid to give the corresponding triazole-containing derivatives after purification by flash chromatography or HPLC. Click chemistry was successfully used to synthesize triazole-containing derivatives of the Pittsburgh compound. Preparation of [18F]fluorinated triazole-containing derivatives, as PET imaging probes is in progress. The compounds will be used in imaging of transgenic mouse model of AD treated with quetiapine, a drug which is known to remove plaques, to determine the drug's effectiveness in treating AD mice.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".