Synthesis and Characterization of Thallium-Texaphyrin Nanoparticles and Their Assessment as Potential Delivery Systems for Auger Electron-Emitting <sup>201</sup>Tl to Cancer Cells
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Thallium-201 is an Auger electron-emitting radionuclide with significant potential for targeted molecular radiotherapy of cancer. It stands out among other Auger electron emitters by releasing approximately 37 Auger and Coster–Kronig electrons per decay, which is one of the highest numbers in its category. It has also a convenient half-life of 73 h, a stable daughter product, established production methods, and demonstrated high in vitro radiotoxicity. However, its full potential in targeted radiotherapy remains unexplored, primarily due to the lack of available efficient chelators for [ 201 Tl]Tl + or [ 201 Tl]Tl 3+ . This study aims to assess texaphyrin for macrocycle chelation of [ 201 Tl]Tl 3+ . Texaphyrins are known for effective binding of trivalent metals with similar ionic radii, such as indium and gadolinium. Optimization of [ 201 Tl]Tl + to [ 201 Tl]Tl 3+ oxidation and subsequent chelation with texaphyrin-lipid conjugate were assessed using thin-layer chromatography. The formation and stability of nonradioactive Tl-texaphyrin-lipid complexes were confirmed by UV–Vis spectroscopy and ultrahigh performance liquid chromatography–mass spectrometry. [ 201 Tl]Tl/Tl-texaphyrin-lipid nanoparticles (nanotexaphyrins) were assembled by using a microfluidic system, and their morphology and stability were evaluated by using dynamic light scattering and transmission electron microscopy. The uptake of these nanotexaphyrins in lung cancer and ovarian cancer cells was evaluated using both radioactive and nonradioactive methods. The conversion of [ 201 Tl]Tl + to [ 201 Tl]Tl 3+ in 0.25 M HCl achieved an average yield of 91.8 ± 3.1%, while the highest radiolabeling yield of the texaphyrin-lipid with [ 201 Tl]Tl 3+ was 25.5 ± 4.5%. Tl-texaphyrin-lipid conjugates were stable at room temperature for at least 72 h. These conjugates were successfully assembled into homogeneous nanotexaphyrins with an average hydrodynamic diameter of 147.4 ± 1.4 nm. Throughout a 72 h period, no changes in size or polydispersity of the synthesized nanoparticles were observed. [ 201 Tl]Tl-nanotexaphyrins were synthesized with an average radiochemical purity of 77.4 ± 10.3% and a yield of 5.1 ± 4.4%. The release of [ 201 Tl]Tl + from [ 201 Tl]Tl-nanotexaphyrins in phosphate-buffered saline exhibited a time- and temperature-dependent pattern, with a faster release observed at 37 °C than at room temperature. Additionally, the uptake of Tl-nanotexaphyrins and [ 201 Tl]Tl-nanotexaphyrins in cancer cells was similar to that of unbound Tl + and [ 201 Tl]Tl + . This is the first time that texaphyrins have been investigated as chelators for radiothallium. Although [ 201 Tl]Tl-nanotexaphyrins were found to be thermodynamically and kinetically unstable, we successfully synthesized stable texaphyrin-lipid complexes with nat Tl 3+ . This opens up opportunities for further refinements in the nanotexaphyrin-lipid structure to enhance [ 201 Tl]Tl 3+ stability and prevent its reduction to a 1+ oxidation state. Future research should consider further modifications to the texaphyrin structure or using texaphyrins without the lipid component.
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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".