Nuclear localizing sequences: an innovative way to improve targeted radiotherapy.

摘要

Systemic targeted radiotherapy is an evolving and promising modality of cancer treatment. The goal of systemic targeted radiotherapy is to be efficacious, yet with minimal normal tissue toxicity. The key characteristic of systemic targeted radiotherapy is that a molecule (antibody, antibody fragment, or peptide) can deliver higher amounts of a radionuclide to cancer cells than to normal tissue. Unlike chemotherapy, systemic targeted radiotherapy is cancer cell specific.The radiopharmaceutical used by Chen et al. (i) in this issue of The Journal of Nuclear Medicine is mIn-DTPA-NLS-HuM195 (DTPA is dieth-ylenetriaminepentaacetic acid; NLS isnuclear localizing sequence). HuM195 is a humanized IgGl monoclonal antibody (mAb) that targets the CD33 antigen on acute myeloid leukemia cells. By itself, HuM195 is not toxic but it effectuates cell killing as a toxin carrier. HuM195 is in current clinical use as Mylotarg (Wyeth-Ayerst; HuM195 conjugated with gemtuzumab ozogamicin, a chemotherapy agent). Despite the enticing ability to target leukemia cells with Mylotarg, the complete response rate is only 26% and patients who do respond ultimately relapse