TAT-10: Directing Alpha-emitting Conjugates to Cancer Chromatin via PARP-1

Kanazawa, Japan (UroToday.com) Poly (ADP-ribose) Polymerase (PARP-1) is a very abundant nuclear protein. High risk neuroblastoma over-expresses PARP-1 and we plan to use this feature to selectively target the neuroblastoma in treating the cancer chromatin. At211-MM4 was evaluated in vitro for the pharmacology and cytotoxicity in a panel of neuroblastoma cell lines.

IMR-05, SK-N-SH and NLF were the most sensitive cell line whereas Be-2-c was the most resistant. At211-MM4 therapy showed significant DNA damage as measured by gH2AX.  Interestingly therapy caused the most resistant cell line Be-2-c to increase PARP-1 expression. As expected, IMR-05 results in vitro translated into the highest therapeutic efficacy in in vivo models.

Presented By: Mehran Makvandi from University of Pennsylvania Perelman School of Medicine, Department of Radiology and Division of Nuclear Medicine

Written By: William Carithers, Lawrence Berkeley National Laboratory

at the 10th International Symposium on Targeted Alpha Therapy (TAT-10)  May 31 - June 1, 2017 - Kanazawa, Japan.