Melissa Deri


Assistant Professor



Department of Chemistry


Lehman College CUNY


250 Bedford Park Blvd West
Bronx, NY 10468



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


Journal article


M. Deri, S. Ponnala, P. Kozlowski, Benjamin P. Burton‐Pye, Huseyin T. Cicek, Chunhua T. Hu, Jason S. Lewis, L. Francesconi
Bioconjugate chemistry, 2015

Semantic Scholar DOI PubMed
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APA
Deri, M., Ponnala, S., Kozlowski, P., Burton‐Pye, B. P., Cicek, H. T., Hu, C. T., … Francesconi, L. (2015). p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET. Bioconjugate Chemistry.

Chicago/Turabian
Deri, M., S. Ponnala, P. Kozlowski, Benjamin P. Burton‐Pye, Huseyin T. Cicek, Chunhua T. Hu, Jason S. Lewis, and L. Francesconi. “p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.” Bioconjugate chemistry (2015).

MLA
Deri, M., et al. “p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.” Bioconjugate Chemistry, 2015.


Abstract

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 derivative, p-SCN-Bn-HOPO, for conjugation to an antibody. A Zr-HOPO crystal structure was obtained showing that the Zr is fully coordinated by the octadentate HOPO ligand, as expected, forming a stable complex. p-SCN-Bn-HOPO was synthesized through a novel pathway. Both p-SCN-Bn-HOPO and p-SCN-Bn-DFO were conjugated to trastuzumab and radiolabeled with (89)Zr. Both complexes labeled efficiently and achieved specific activities of approximately 2 mCi/mg. PET imaging studies in nude mice with BT474 tumors (n = 4) showed good tumor uptake for both compounds, but with a marked decrease in bone uptake for the (89)Zr-HOPO-trastuzumab images. Biodistribution data confirmed the lower bone activity, measuring 17.0%ID/g in the bone at 336 h for (89)Zr-DFO-trastuzumab while (89)Zr-HOPO-trastuzumab only had 2.4%ID/g. We successfully synthesized p-SCN-Bn-HOPO, a bifunctional derivative of 3,4,3-(LI-1,2-HOPO) as a potential chelator for (89)Zr. In vivo studies demonstrate the successful use of (89)Zr-HOPO-trastuzumab to image BT474 breast cancer with low background, good tumor to organ contrast, and, importantly, very low bone uptake. The reduced bone uptake seen with (89)Zr-HOPO-trastuzumab suggests superior stability of the (89)Zr-HOPO complex.


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