Carboxylic- and Amide Donor-Functionalized Pyridine- <i>N</i> - <i>trans</i> -Substituted Cyclen-Based Chelators for <sup>203</sup> Pb/ <sup>212</sup> Pb Theranostic Radiopharmaceuticals
Bibliographic record
Abstract
The element-equivalent theranostic pair lead-203 ( 203 Pb, 100% EC, t 1/2 = 51.92 h) and lead-212 ( 212 Pb, 100% β – to α emitting 212 Bi, t 1/2 = 10.64 h) enable both diagnostic imaging and targeted therapy of disease within a single chemical framework through the emission of γ-rays and α-particles, respectively. In efforts to further advance the clinical potential of this theranostic pair, we report the synthesis and evaluation of two N 1, N 7 ( N-trans )-symmetrical cyclen-based chelators─DO2A-2Py and DCMC-2Py─designed to form thermodynamically stable and kinetically inert Pb 2+ complexes. Protonation and stability constants determined by pH-dependent 1 H NMR titrations revealed that [Pb(DO2A-2Py)] and [Pb(DCMC-2Py)] 2+ form complexes with high thermodynamic stability (logβ [Pb(DO2A-2Py)] = 22.05 ± 0.05 and logβ [Pb(DCMC-2Py)] 2+ = 18.62 ± 0.05). Structural analysis by single crystal X-ray diffractometry revealed eight-coordinate Pb 2+ complexes with the expected trans arrangement. Quantitative radiolabeling of [ 203 Pb]Pb 2+ was achieved for both DO2A-2Py and DCMC-2Py under mild, highly dilute reaction conditions (pH 7, 10 min reaction time). The resulting complexes exhibited remarkable kinetic inertness in serum, and in the presence of excess Pb 2+ or EDTA, over 52 h, remaining >96% ([ 203 Pb]Pb 2+ -DO2A-2Py) and >94% ([ 203 Pb]Pb 2+ -DCMC-2Py) intact. Together, these findings reveal DO2A-2Py and DCMC-2Py as highly promising chelators for [ 203/212 Pb]Pb 2+ radiopharmaceuticals.
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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 | 0.000 | 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) | 0.001 | 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 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".