Radiolabeled (R) ‐(–)‐5‐iodo‐3'‐O‐[2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl]‐2'‐deoxyuridine: a new theranostic for neuroblastoma

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 ofMYCN, 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‐[125I]iodo ‐3'‐O‐[2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl]‐2'‐deoxyuridine (9, GPAID) was designed. This compound enters neuroblastoma cells much like meta ‐iodobenzylguanidine (MIBG). Additionally, it co‐targets DNA of proliferating cells, an attribute especially advantageous in the treatment ofMYCN‐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 nonradioactive MIBG. The intracellular processing and DNA targeting properties were confirmed in the subcellular distribution experiments. Studies in a mouse model of neuroblastoma demonstrated the therapeutic potential o...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research