We have demonstrated that — 3,4,3-(LI-1,2-HOPO) or HOPO— which has four 1,2-hydroxypyridinone groups for metal binding and comes from the actinide sequestration literature, binds to 89Zr with high efficiency and stability. We reported the bifunctional variant, p-SCN-Bn-HOPO, that can be conjugated to antibodies via the isothiocyanate group and radiolabeled with 89Zr at room temperature. In vivo studies demonstrated that 89Zr-HOPO-trastuzumab images breast cancer with low background, good tumor to organ contrast, and, importantly very low bone uptake. Thus, p-SCN-Bn-HOPO is a very desirable bifunctional chelator for radioimmunoPET imaging using 89ZrHowever the reported synthesis of p-SCN-Bn-HOPO involves 9 steps, multiple HPLC purifications with an overall yield of about 1.5%. We thus used a different methodology to synthesize p-SCN-Bn-HOPO in three steps with improvements in yields by 10 fold. Here-in we are going to present detailed synthesis of p-SCN-Bn-HOPO resulting in 15% overall yield.

Improved synthesis of p-SCN-Bn-HOPO for 89Zr chelation

2019 Fall National Meeting

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