Tumor Therapy with Targeted Atomic Nanogenerators

TLDR

A single high‑linear‑energy‑transfer alpha particle can kill a target cell, and nanogenerators targeting a wide variety of cancers may be possible. The study develops methods to target molecular‑sized generators of alpha‑emitting isotope cascades to the interior of cancer cells using actinium‑225 coupled to internalizing monoclonal antibodies. These methods involve coupling actinium‑225 to internalizing monoclonal antibodies to deliver alpha‑emitting isotope cascades into cancer cells. In vitro, the constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at picocurie levels, and in vivo, single‑dose injections at nanocurie levels induced tumor regression and prolonged survival in mice with solid prostate carcinoma or disseminated human lymphoma without toxicity.

Abstract

A single, high linear energy transfer alpha particle can kill a target cell. We have developed methods to target molecular-sized generators of alpha-emitting isotope cascades to the inside of cancer cells using actinium-225 coupled to internalizing monoclonal antibodies. In vitro, these constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at becquerel (picocurie) levels. Injection of single doses of the constructs at kilobecquerel (nanocurie) levels into mice bearing solid prostate carcinoma or disseminated human lymphoma induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of animals. Nanogenerators targeting a wide variety of cancers may be possible.