Title:Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer
Volume: 6
Issue: 2
Author(s): Sean L. Kitson, Vincenzo Cuccurullo, Thomas S. Moody and Luigi Mansi
Affiliation:
Keywords:
Targeted alpha therapy (TAT), radionuclide antibody-conjugates (RACs), radionuclide generators, alpha particle,
monoclonal antibodies, tumour-anti-vascular-alpha-therapy (TAVAT).
Abstract: Targeted alpha therapy (TAT) is an investigational procedure which utilises monoclonal antibodies (mAbs),
peptide conjugates and/or other chemical compounds. These bio-vectors are able to transport a dose of alpha particles to
destroy cancer cells. Radionuclide antibody-conjugates (RACs), labelled with beta emitters, have already been used in
humans. More recently, TAT has been introduced to treat oncological diseases mainly leukaemia and lymphoma. Encouraging
results have also been obtained in solid neoplasms with the administration of anti-tenascin. This chimeric antibody
labelled with astatine-211 was delivered in patients with recurrent brain tumours into a surgically created cavity. Conversely,
a clinical trial using a standard TAT approach to treat patients with metastatic melanoma, observed the shrinkage
of the solid tumour mass. This response in melanoma may lead to an alternative mechanism for TAT, called tumour-antivascular-
alpha-therapy (TAVAT), and forms the basis of a novel approach to the treatment of cancer disease states. In this
paper, we will concentrate mainly on the application of TAT using antibodies. In particular, an investigation into the major
general features connected with the use of alpha emitters in cancer therapy will be discussed. The prospective role of
TAT with RACs will also be outlined briefly, especially focussing on the most important therapeutic strategies to date
based on antibodies radiolabelled with beta emitters.
