Targeted Radionuclide Therapy of Human Tumors

Abstract

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

Keywords: Auger electron; antibody; peptide; radio-immunotherapy; radionuclide; targeted therapy; α-emitter; β-emitter.

Figure 1

A pie chart of the prevalence of cancer treatments.

Figure 2

Schematic representation of ionization density along the path of α-, β-particles, and Auger electrons (α-particles are considered densely-ionizing radiation, β-particles are sparsely ionizing, and Auger electrons form clusters with a high density of ionization).

Figure 3

Schematic representation of conventional and pre-targeted radionuclide therapy. (A) Conventional targeted radionuclide therapy is realized only using monoclonal antibodies or other carrier molecules directly conjugated with a radionuclide; (B) Multi-step pre-targeted radionuclide therapy, “amplifier” mode. At first, antibodies conjugated with streptavidin are used and following antibody binding radiolabelled DOTA-biotin is introduced. It is presumed that each streptavidin molecule binds to four molecules of radionuclide-labeled biotin; (C) Multi-step pre-targeted radionuclide therapy, mode for specificity increase.