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

GPAID was designed to treat high ‐risk neuroblastoma, including relapsed or refractory disease. GPAID targets neuroblastoma cells in the same way as MIBG. It also cotargets DNA of proliferating cells, an attribute especially advantageous in the treatment ofMYCN‐amplified tumors. 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 metaiodobenzylguanidine (MIBG). Additionally, it cotargets 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 ...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research