p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.

@article{Deri2015pSCNBnHOPOAS,
  title={p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.},
  author={Melissa A Deri and Shashikanth Ponnala and Paul Kozlowski and Benjamin P. Burton‐Pye and Huseyin T. Cicek and Chunhua Tony Hu and Jason S. Lewis and Lynn C. Francesconi},
  journal={Bioconjugate chemistry},
  year={2015},
  volume={26 12},
  pages={
          2579-91
        }
}
Zirconium-89 has an ideal half-life for use in antibody-based PET imaging; however, when used with the chelator DFO, there is an accumulation of radioactivity in the bone, suggesting that the (89)Zr(4+) cation is being released in vivo. Therefore, a more robust chelator for (89)Zr could reduce the in vivo release and the dose to nontarget tissues. Evaluation of the ligand 3,4,3-(LI-1,2-HOPO) demonstrated efficient binding of (89)Zr(4+) and high stability; therefore, we developed a bifunctional… 

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References

SHOWING 1-10 OF 48 REFERENCES

Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents and lead to a safer PET tracer with reduced background radiation dose.

H6phospa-trastuzumab: bifunctional methylenephosphonate-based chelator with 89Zr, 111In and 177Lu.

It can be concluded from this work that H6phospa is not superior to the previously studied H4octapa for use with (111)In and (177)Lu, but improvements in (89)Zr radiolabeling were observed over H4 octapa, suggesting H6 phospa to be an excellent starting point for elaboration of (89]Zr-based radiopharmaceutical development.

Novel Bifunctional Cyclic Chelator for 89Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates

Findings indicate that FSC is a highly promising chelator for the development of 89Zr-based PET imaging agents.

Rational design, synthesis, and evaluation of tetrahydroxamic acid chelators for stable complexation of zirconium(IV).

A series of tetrahydroxamic acids of varying geometries are designed for improved complexation of (89) Zr, with the best chelators providing dramatically improved stabilities compared with the reference DFB.

Impact of bifunctional chelators on biological properties of 111In-labeled cyclic peptide RGD dimers

It was concluded that 111In(DTPA-3P-RGD2) can be an effective integrin αvβ3-targeted radiotracer if the high-specific activity is required and DOTA remains to be the BFC of choice for the development of therapeutic lanthanide drugs.

Hydroxypyridinonate complex stability of group (IV) metals and tetravalent f-block elements: the key to the next generation of chelating agents for radiopharmaceuticals.

High thermodynamic stabilities not only confirm the unparalleled Pu(IV) affinity of 3,4,3-LI(1,2-HOPO) as a decorporation agent but also corroborate the great potential of hydroxypyridinonate ligands as new (89)Zr-chelating platforms for immuno-PET applications.

Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89.

The first octadentate terephthalamide ligands, which are easily radiolabeled with (89)Zr and are highly stable in vitro, represent a novel class of chelators, which is worthy of further development as BFCs for (89]Zr.

Evaluation of desferal as a bifunctional chelating agent for labeling antibodies with Zr-89.

A practical guide to the construction of radiometallated bioconjugates for positron emission tomography.

A practical guide to the construction of radiometal-based PET bioconjugates, in which the design choices and synthetic details of a wide range of biomolecular tracers from the literature are collected in a single reference.