Radiolabeled (R)-(-)-5-iodo-3'-O-[2-(ε-guanidinohexanoyl)-2-phenylacetyl]-2'-deoxyuridine: A new theranostic for neuroblastoma.

Journal of Labelled Compounds & Radiopharmaceuticals
Zbigniew P KortylewiczJanina Baranowska-Kortylewicz

Abstract

Neuroblastoma, the most common extracranial solid tumor in children, accounts for nearly 8% of childhood cancers in the United States. It is a disease with pronounced clinical and biological heterogeneities. The amplification of MYCN, whose key tumorigenic functions include the promotion of proliferation, facilitation of the cell's entry into the S phase, and prevention of cells from leaving the cell cycle, correlates with poor prognosis. Patients with a high proliferation index disease have low survival rates. Neuroblastoma is one of the most radioresponsive of all human tumors. To exploit this radiosensitivity, radioactive guanidine (R)-(-)-5-[125 I]iodo-3'-O-[2-(ε-guanidinohexanoyl)-2-phenylacetyl]-2'-deoxyuridine (9, GPAID) was designed. This compound enters neuroblastoma cells much like metaiodobenzylguanidine (MIBG). Additionally, it cotargets DNA of proliferating cells, an attribute especially advantageous in the treatment of MYCN-amplified tumors. GPAID was synthesized from the trimethylstannyl precursor with an average yield of >90% at the no-carrier-added specific activities. The norepinephrine transporter-aided delivery of GPAID to neuroblastoma cells was established in the competitive uptake studies with nonradioact...Continue Reading

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Citations

Jun 3, 2020·International Journal of Molecular Sciences·Andrea CiminiOrazio Schillaci
May 1, 2021·Journal of Personalized Medicine·Atia SamimBart de Keizer

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