PMID: 26807322Jan 26, 2016Paper

Tumor-selective anti-cancer effects of the synthetic alkyl phosphocholine analog CLR1404 in neuroblastoma

American Journal of Cancer Research
Roberta MarinoMario Otto

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in children and is associated with high mortality in advanced stages. Survivors suffer from long-term treatment-related sequelae. Thus, new targeted treatment options are urgently needed. 18-(p-[(127)I] iodophenyl) octadecyl phosphocholine (CLR1404) is a novel, broadly tumor targeted small molecule drug suitable for intravenous injection with highly selective tumor uptake. As a carrier molecule for radioactive iodine, CLR1404 is in clinical trials as cancer imaging agent and radiotherapeutic drug. Chemically, CLR1404 belongs to the anti-tumor alkyl phospholipids, a class of drugs known to have intrinsic cytotoxic effects on cancer cells. Therefore, we hypothesized that CLR1404 could be a tumor-targeted anti-cancer agent for neuroblastoma, and investigated its effect in vitro and in vivo. CLR1404 was taken up by NB cells in a highly tumor-selective manner both in vitro and in vivo, confirmed by flow cytometry and PET/CT imaging of mouse flank xenografts with (124)I-CLR1404, respectively. Using flow cytometry, MTT assay, Western blotting and caspase 3/7 assay, we confirm that in vitro treatment with CLR1404 leads to robust apoptosis and cell death in multiple NB cell ...Continue Reading

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