A Second Generation Mn-Porphyrin Dimer with a Twisted Linker as a Potential Blood Pool Agent for MRI: Tuning the Geometry and Binding with HSA
Bibliographic record
Abstract
Blood-pool agents (BPAs) are MRI contrast agents (CAs) characterized by their long circulation in the vascular system to provide an extended time window for high-resolution MR angiography (MRA). Prolonged vascular retention, however, impedes the excretion of BPAs. Therefore, chemical strategy to regulate the balance between retention and clearance is important to reach optimal pharmacokinetics. We recently developed MnP2, the first Mn(III)-porphyrin (MnP) based BPA. MnP2 shows high T1 relaxivity (r1) and high affinity to human serum albumin (HSA) that leads to up to 48-h vascular retention in rats. However, upon albumin binding, the r1 is decreased. To modulate vascular retention time and plasma r1, a regioisomer of MnP2, m-MnP2, was synthesized. The free m-MnP2 exhibits lower r1 than that of MnP2 at magnetic fields above 2 MHz, which agrees with their relative hydrodynamic sizes. The HSA binding of m-MnP2 was evaluated using UV-Vis spectroscopy and found to have tuned-down affinity in comparison with MnP2. Upon HSA binding, the protein complex of m-MnP2 exhibits an r1 of 11.8 mM−1 s−1 at 3 T, which is higher than that of MnP2 bound to HSA. Taken together, this demonstrated the role of molecular geometry in optimizing the pharmacokinetics of albumin-targeting BPAs.
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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) | 0.001 | 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".