Tumor immunotargeting using innovative radionuclides

Abstract

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

Figure 1

The concept of pretargeting with the Affinity Enhancement System: a bispecific antibody, designed to bind by one arm a tumor antigen (e.g., carcinomembryonic antigen) and by the other a hapten (e.g., the indium-diethylene triamine pentaacetic acid (DTPA) complex or the histamine-succinyl-glutamine (HSG) pseudo-peptide), is injected first. It distributes in the whole-body and targets the tumor cells. After an interval of several hours to a few days, the radiolabeled bivalent hapten is injected. It binds rapidly to the tumor. At the tumor cell surface, hapten bivalency induces cooperativity, resulting in very slow release.

Figure 2

Images recorded in a patient with a carcino-embryonic antigen (CEA)-positive lung carcinoma treated by pretargeted radioimmunotherapy using the TF2 anti-CEA bispecific antibody and the ¹⁷⁷Lu-IMP288 peptide. Image shows a good targeting of the lung tumor.

Figure 3

Positron emission tomography (PET) in a patient with a relapse of medullary thyroid carcinoma recorded after injection of the TF2 anti-carcino-embryonic antigen (CEA) bispecific antibody and the ⁶⁸Ga-IMP-288 peptide. Image shows a good detection of a bone lesion.

Figure 4

Imaging performed in a patient with a metastatic breast carcinoma. (A) Immuno-PET performed using the TF2 anti-CEA bispecific antibody and the ⁶⁸Ga-IMP-288 peptide detects a more diffuse bone marrow involvement that FDG-PET (B).