Metal Chelators for Oligonucleotide Modification

DOTA and NOTA are macrocyclic chelators with very high stability in vivo, ideal for PET/SPECT radionuclides. DTPA is acyclic, easier to use, but less stable long-term. Choice depends on isotope (e.g., ⁶⁸Ga favors NOTA; ¹⁷⁷Lu favors DOTA; ¹¹¹In often uses DTPA).

DFO (Desferrioxamine) is the gold-standard chelator for ⁸⁹Zr immunoPET. It binds Zr⁴⁺ strongly and is widely used for antibody and oligo conjugates that need Zr-based imaging.

DPA complexes zinc most strongly (Zn²⁺–DPA), and is used in phosphate-recognition probes. It can also bind Cu²⁺/Mn²⁺ but is not suitable for long-term therapeutic radionuclide labeling.

Most chelators are supplied with active handles (NHS esters for amines, isothiocyanates, maleimides for thiols, azide/alkyne for click). They are typically conjugated at the 5′ or 3′ terminus using linkers to reduce steric interference with hybridization.

Terminal modifications usually have little effect on T_m. Internal chelator insertions may destabilize duplexes depending on linker length and placement. Using PEG spacers helps minimize impact.

DOTA (¹⁷⁷Lu, ⁹⁰Y), NOTA (⁶⁸Ga, ⁶⁴Cu), and CB-TE2A (⁶⁴Cu) are widely used for therapy. The choice depends on isotope coordination chemistry and required in-vivo stability.

Yes. Many designs use orthogonal handles (amine, thiol, click) to add both a chelator and a dye/peptide/lipid. Careful spacing with PEG linkers reduces quenching or steric conflicts.

QC typically includes ESI-MS or MALDI-TOF for identity, HPLC for purity, and ICP-MS or radioactivity assays to confirm metal incorporation. CoA reports yield, purity %, and conjugation details.

Lyophilized: store at −20 °C. In solution: use metal-free buffer, aliquot to avoid freeze-thaw, and avoid contamination with adventitious metals. Protect from light if dyes are also included.