Simplifying “SiFA”: A High-Yielding, Automated Protocol for the One-Step Radiosynthesis of the Neuroendocrine Tumor Imaging Agent [ <sup>18</sup> F]SiTATE <i>via</i> a Merging of “Silicon-Fluoride Acceptor” (SiFA) and “Nonanhydrous, Minimally Basic” (NAMB) Chemistries
Bibliographic record
Abstract
Developing radiochemical strategies that enable the simple, rapid, and high-yielding incorporation of radioisotopes into bioactive targeting vectors using sterile, cassette-based kits is critical to sustaining clinical practice and advancing radiopharmaceutical research. 18 F-bearing positron emission tomography (PET) imaging radiopharmaceuticals that use functionally-complex biomolecules as targeting vectors are particularly challenging to synthesize because they are sensitive to the elevated temperatures and basic conditions traditionally used to incorporate [ 18 F]fluoride, necessitating complex, low-yielding multistep radiolabeling strategies using 18 F-prosthetic groups. Direct 18 F-labeling of bioactive peptides can be achieved through 19 F-for- 18 F exchange of di- tert -butylphenylfluorosilane pendant groups (a.k.a. “SiFA” chemistry). However, the translation of such protocols to automated synthesis units, which are required for the clinical production of 18 F-radiopharmaceuticals, has been hampered by the incompatibility of SiFAylated 19 F-peptide precursors with current methods to isolate [ 18 F]F – on anion exchange sorbents, including azeotropic distillation of aqueous eluates containing (bi)carbonate base, or the extraction of [ 18 F]F – via strongly-basic Kryptofix-222/KOH complex. Nonbasic tetraalkylammonium salts can be used to release [ 18 F]F – from anion exchange cartridges in small volumes of water directly into vessels containing radiolabeling precursors in MeCN or DMSO [a.k.a. nonanhydrous, minimally basic (‘NAMB’) 18 F chemistry]; these “damp” reaction mixtures (1–6% water) can be heated to achieve traditional nucleophilic 18 F-fluorinations, or, as we report here, high-yielding SiFA reactions. This merging of SiFA and NAMB is reported here first for the one-step, manual radiosynthesis of [ 18 F]SiTATE, a clinically-validated neuroendocrine tumor imaging agent, and then later translated to the FASTlab 1 automated synthesis platform. An exceptionally high non-decay-corrected radiochemical yield (NDC-RCY; 50 ± 6%, n = 4) was obtained after admixing of 19 F-precursor (50 nmol) with tetrabutylammonium dihydrogen phosphate/tetrabutylammonium [ 18 F]fluoride in 44:50:6 MeCN:DMSO:H 2 O (1 mL) for 10 min at ambient temperature. Radiochemical purity was 95% after the purification of 18 F-peptide by solid-phase extraction. The highest activity yield produced from a single cyclotron bombardment was 594 mCi (52% NDC-RCY; 440 GBq/μmol), suggesting that this ultrasimple and efficient automated protocol is amenable to the production of multiple patient doses from a single batch of [ 18 F]fluoride.
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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.005 |
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 source (direct Gemma or distilled Codex), 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".